Non-human animals having an engineered immunoglobulin lambda light chain and uses thereof

Abstract

This invention provides non-human animals (and / or non-human cells) and methods of using them, the non-human animals (and / or non-human cells) having a genome containing sequences encoding human antibodies (i.e., immunoglobulin genes). The non-human animals described herein exhibit antibodies containing immunoglobulin (Ig) light chains, characterized by the presence of a human Vλ domain. In some embodiments, the non-human animals described herein are characterized by exhibiting antibodies containing a human Vλ light chain (encoded by a human Igλ light chain-coding sequence inserted into the endogenous Igκ light chain locus of the non-human animal). A method for producing antibodies from non-human animals is also provided, the antibodies containing a human variable region and a mouse constant region.

Description

Non-human animals with engineered immunoglobulin lambda light chains and uses thereof [Cross-reference to related applications] This application claims priority to U.S. Provisional Application No. 62 / 594,944, filed on December 5, 2017; U.S. Provisional Application No. 62 / 594,946, filed on December 5, 2017; U.S. Provisional Application No. 62 / 609,241, filed on December 21, 2017; and U.S. Provisional Application No. 62 / 609,251, filed on December 21, 2017; each of which is incorporated herein by reference. The present invention provides non-human animals (and / or non-human cells) having a genome comprising sequences encoding human antibodies (i.e., immunoglobulin genes) and methods of using the same. The non-human animals described herein express antibodies comprising immunoglobulin (Ig) light chains characterized by the presence of human Vλ domains. The non-human animals described herein, in some embodiments, are characterized by the expression of antibodies comprising human Vλ light chains encoded by human Igλ light chain-encoding sequences inserted into the non-human animal's endogenous Igκ light chain locus. Methods of producing antibodies comprising human variable regions and mouse constant regions from non-human animals are also provided. Human antibodies are the fastest-growing class of therapeutics. Among current technologies for antibody production, the development of genetically modified animals (e.g., rodents) harboring genetic material encoding human antibodies (in whole or in part) has revolutionized the field of human therapeutic monoclonal antibodies for the treatment of various diseases. There remains a need for improved in vivo systems for the production of human monoclonal antibodies that maximize the human antibody repertoire in host genetically modified animals. In some embodiments, the present invention provides a rodent having a germline genome comprising: An engineered endogenous immunoglobulin kappa light chain locus comprising: (a) one or more human Vλ gene segments, (b) one or more human Jλ gene segments, and (c) one or more Cλ genes, wherein the one or more human Vλ gene segments and the one or more human Jλ gene segments are operably linked to the one or more Cλ genes, and wherein the rodent lacks a rodent CK gene at the engineered endogenous immunoglobulin κ locus. In some embodiments, the one or more Cλs are Cλ genes. In some embodiments, a Cλ gene is or comprises a rodent Cλ gene. In some embodiments, the rodent Cλ gene has a sequence that is at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% identical to a mouse Cλ1, mouse Cλ2, or mouse Cλ3 gene. In some embodiments, the rodent Cλ gene is or comprises a mouse Cλ1 gene. In some embodiments, the rodent Cλ gene is or comprises a rat Cλ gene. In some embodiments, the rat Cλ gene has a sequence that is at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% identical to a rat Cλ1, rat Cλ2, rat Cλ3, or rat Cλ4 gene. In some embodiments, one or more human Vλ gene segments and one or more human Jλ gene segments replace one or more rodent Vκ gene segments, one or more rodent Jκ gene segments, or any combination thereof. In some embodiments, one or more human Vλ gene segments and one or more human Jλ gene segments replace one or more rodent Vκ gene segments, one or more rodent Jκ gene segments, or any combination thereof. In some embodiments, one or more human Vλ gene segments and one or more human Jλ gene segments replace all functional rodent Vκ gene segments and / or all functional rodent Jκ gene segments. In some embodiments, the one or more human Vλ gene segments include Vλ4-69, Vλ8-61, Vλ4-60, Vλ6-57, Vλ10-54, Vλ5-52, Vλ1-51, Vλ9-49, Vλ1-47, Vλ7-46, Vλ5-45, Vλ1-44, Vλ7-43, Vλ1-40, Vλ5-39, Vλ5-37, Vλ1-36, Vλ3-27, Vλ3-25, Vλ2-23, Vλ3-22, Vλ3-21, Vλ3-19, Vλ3-16, Vλ2-14, Vλ3-12, Vλ2-11, Vλ3-10, Vλ3-9, Vλ2-8, Vλ4-3, Vλ3-1, or any combination thereof. In some embodiments, the one or more human Vλ gene segments include Vλ4-69, Vλ8-61, Vλ4-60, Vλ6-57, Vλ10-54, Vλ5-52, Vλ1-51, Vλ9-49, Vλ1-47, Vλ7-46, Vλ5-45, Vλ1-44, Vλ7-43, Vλ1-40, Vλ3-27, Vλ3-25, Vλ2-23, Vλ3-22, Vλ3-21, Vλ3-19, Vλ3-16, Vλ2-14, Vλ3-12, Vλ2-11, Vλ3-10, Vλ3-9, Vλ2-8, Vλ4-3, Vλ3-1, or any combination thereof. In some embodiments, the one or more human Vλ gene segments include Vλ4-69, Vλ8-61, Vλ4-60, Vλ6-57, Vλ10-54, Vλ5-52, Vλ1-51, Vλ9-49, Vλ1-47, Vλ7-46, Vλ5-45, Vλ1-44, Vλ7-43, Vλ1-40, Vλ5-39, Vλ5-37, Vλ1-36, Vλ3-27, Vλ3-25, Vλ2-23, Vλ3-22, Vλ3-21, Vλ3-19, Vλ3-16, Vλ2-14, Vλ3-12, Vλ2-11, Vλ3-10, Vλ3-9, Vλ2-8, Vλ4-3, and Vλ3-1. In some embodiments, the one or more human Jλ gene segments include Jλ1, Jλ2, Jλ3, Jλ6, Jλ7, or any combination thereof. In some embodiments, the one or more human Jλ gene segments include Jλ1, Jλ2, Jλ3, Jλ6, and Jλ7. In some embodiments, the modified endogenous immunoglobulin κ light chain locus includes one or more human Vλ non-coding sequences, each of which is adjacent to at least one of one or more human Vλ gene segments, wherein the one or more human Vλ non-coding sequences are human Vλ gene segments that naturally occur adjacent to the endogenous human immunoglobulin λ light chain locus. For example, referring to FIG. 20 , the first exemplary endogenous human Vλ non-coding sequence naturally occurs adjacent to (and 3' to) the Vλ3-12 gene segment of the endogenous human immunoglobulin λ light chain locus. A modified endogenous immunoglobulin κ light chain locus (including the first exemplary endogenous human Vλ non-coding sequence) can include the non-coding sequence adjacent to (and 3' to) the Vλ3-12 gene segment of the endogenous human immunoglobulin κ light chain locus. A modified endogenous immunoglobulin κ light chain locus (including the first exemplary endogenous human Vλ non-coding sequence) may include the non-coding sequence near (and located 5' to) the Vλ2-11 gene segment of the endogenous human immunoglobulin κ light chain locus. In some embodiments, the modified endogenous immunoglobulin κ light chain locus (including the first exemplary endogenous human Vλ non-coding sequence) may also include the non-coding sequence near (preferably located 3' to) the Vλ3-12 gene segment of the endogenous human immunoglobulin λ light chain locus, and near (preferably located 5' to) the V2-11 gene segment of the endogenous human immunoglobulin κ light chain locus. In some embodiments, each of the one or more human Vλ non-coding sequences is or includes an intron. In some embodiments, the engineered endogenous immunoglobulin κ light chain locus comprises one or more human Jλ non-coding sequences, each of which is adjacent to at least one of the one or more human Jλ gene segments, wherein the one or more human Jλ non-coding sequences naturally occur adjacent to the human Jλ gene segment of the endogenous human immunoglobulin κ light chain locus. In some embodiments, each of the one or more human Jλ non-coding sequences is or comprises an intron. In some embodiments, the engineered endogenous immunoglobulin κ light chain locus comprises one or more human Jκ non-coding sequences, each of which is adjacent to at least one of the one or more human Jλ gene segments, wherein the one or more human Jκ non-coding sequences naturally occur adjacent to the human Jκ gene segment of the endogenous human immunoglobulin κ light chain locus. For example, referring to FIG. 21 , a first exemplary endogenous human Jκ non-coding sequence naturally occurs at the endogenous human immunoglobulin κ light chain locus. The modified endogenous immunoglobulin κ light chain locus comprising the first exemplary endogenous human Jκ non-coding sequence can be a non-coding sequence located adjacent to a Jλ gene segment (e.g., Jλ1, Jλ2, Jλ3, Jλ6, or Jλ7) in the modified endogenous immunoglobulin κ light chain locus. In some embodiments, each of the one or more human Jκ non-coding sequences is or comprises an intron. In some embodiments, the modified endogenous immunoglobulin κ light chain locus comprises one or more human Vλ non-coding sequences, wherein each of the one or more human Vλ non-coding sequences is adjacent to Vλ4-69, Vλ8-61, Vλ4-60, Vλ6-57, Vλ10-54, Vλ5-52, Vλ1-51, Vλ9-49, Vλ1-47, Vλ7-46, Vλ5-45, Vλ1-44, Vλ7-43, Vλ1-40, Vλ5-39, Vλ5-37, Vλ1-36, Vλ3-27, Vλ 3-25, Vλ2-23, Vλ3-22, Vλ3-21, Vλ3-19, Vλ3-16, Vλ2-14, Vλ3-12, Vλ2-11, Vλ3-10, Vλ3- 9, Vλ2-8, Vλ4-3, or Vλ3-1, and wherein each of the one or more human Vλ non-coding sequences is naturally adjacent to Vλ4-69, Vλ8-61, Vλ4-60, Vλ6-57, Vλ10-54, Vλ5-52, Vλ1-51, Vλ9-49, Vλ1-47, Vλ7-46, Vλ5-45, Vλ1-44, Vλ7-43, Vλ1-40, Vλ5-39, Vλ5-37, Vλ1-36, Vλ3-27, Vλ3-25, Vλ2-23, Vλ3-22, Vλ 3-21, Vλ3-19, Vλ3-16, Vλ2-14, Vλ3-12, Vλ2-11, Vλ3-10, Vλ3-9, Vλ2-8, Vλ4-3, or Vλ3-1. In some embodiments, the engineered endogenous immunoglobulin κ light chain locus comprises one or more human Jλ non-coding sequences, wherein each of the one or more human Jλ non-coding sequences is adjacent to Jλ1, Jλ2, Jλ3, Jλ6, or Jλ7 of the engineered endogenous immunoglobulin κ light chain locus, and wherein each of the one or more human Jλ non-coding sequences naturally occurs adjacent to Jλ1, Jλ2, Jλ3, Jλ6, or Jλ7 of the endogenous human immunoglobulin λ light chain locus. In some embodiments, the engineered endogenous immunoglobulin κ light chain locus comprises one or more human Jκ non-coding sequences, wherein each of the one or more human Jκ non-coding sequences is adjacent to Jλ1, Jλ2, Jλ3, Jλ6, or Jλ7 of the engineered endogenous human immunoglobulin κ light chain locus, and wherein each of the one or more human Jκ non-coding sequences naturally occurs adjacent to Jκ1, Jκ2, Jκ3, Jκ4, or Jκ5 of the endogenous human immunoglobulin κ light chain locus. In some embodiments, the engineered endogenous immunoglobulin κ light chain locus comprises a κ light chain non-coding sequence between the one or more human Vλ gene segments and the one or more human Jλ gene segments. In some embodiments, the κ light chain non-coding sequence is a human κ light chain non-coding sequence. In some embodiments, the human κ light chain non-coding sequence comprises a sequence that naturally occurs between the human Vκ4-1 gene segment and the human Jκ1 gene segment of the endogenous human immunoglobulin κ light chain locus. In some embodiments, the rodent described herein is homozygous for the engineered endogenous immunoglobulin kappa light chain locus. In some embodiments, the rodent described herein is heterozygous for the engineered endogenous immunoglobulin kappa light chain locus. In some embodiments, the rodent's germline genome comprises a second engineered endogenous immunoglobulin kappa light chain locus comprising: (a) one or more human Vκ gene segments, and (b) one or more human Jκ gene segments, The one or more human Vκ gene segments and the one or more human Jκ gene segments are operatively linked to a CK gene. In some embodiments, the rodent's genome further comprises a nucleic acid sequence encoding an exogenous terminal deoxynucleotidyl transferase (TdT) operably linked to a transcriptional control unit. In some embodiments, the transcriptional control unit comprises a RAG1 transcriptional control unit, a RAG2 transcriptional control unit, an immunoglobulin heavy chain transcriptional control unit, an immunoglobulin kappa light chain transcriptional control unit, an immunoglobulin lambda light chain transcriptional control unit, or any combination thereof. In some embodiments, the nucleic acid sequence encoding the exogenous TdT is located in an immunoglobulin kappa light chain locus, an immunoglobulin lambda light chain locus, an immunoglobulin heavy chain locus, a RAG1 locus, or a RAG2 locus. In some embodiments, the TdT is human TdT. In some embodiments, the TdT is a short isoform of TdT (TdTS). In some embodiments, the rodents described herein comprise a nucleic acid sequence encoding an exogenous terminal deoxynucleotidyl transferase (TdT) operably linked to a transcriptional control unit in their germline genome and exhibit a light chain (e.g., a light chain variable domain thereof) that is at least 1.2-fold, at least 1.5-fold, at least 1.75-fold, at least 2-fold, at least 3-fold, at least 4-fold, or at least 5-fold increase in junctional diversity compared to a comparable mouse (e.g., a littermate) that does not comprise an exogenous terminal deoxynucleotidyl transferase (TdT) operably linked to a transcriptional control unit in its germline genome. In some embodiments, junctional diversity is measured as the number of unique CDR3s per 10,000 reads. In some embodiments, the rodents described herein comprise a nucleic acid sequence encoding an exogenous terminal deoxynucleotidyl transferase (TdT) operably linked to a transcriptional control unit in their germline genome, and at least 25%, at least 30%, at least 35%, at least 40%, 45%, at least 50%, at least 55%, at least 60%, at least 65% of the light chains (e.g., lambda and / or kappa light chains) produced by the rodent have non-templated incorporation. In some embodiments, the rodent germline genome described herein comprises: An engineered endogenous immunoglobulin heavy chain locus comprising: (a) One or more human V H gene fragments, (b) one or more human D H gene fragments, and (c) one or more human J H gene fragments, wherein the one or more human V H Gene fragments, one or more human D H gene fragments, and one or more human J H The gene segment is operatively linked to a rodent immunoglobulin heavy chain constant region at the modified endogenous immunoglobulin heavy chain locus. In some embodiments, one or more human V H Gene fragments, one or more human D H gene fragments, and one or more human J H gene segments located between one or more rodent VH gene segments, one or more rodent D H Gene fragments, one or more rodent J H In some embodiments, the one or more human V H Gene fragments, one or more human D H gene fragments, and one or more human J H Gene fragments that replace one or more rodent V H Gene fragments, one or more rodent D H Gene fragments, one or more rodent J H gene fragments, or any combination thereof. In some embodiments, the one or more human V H Gene segments include V H 3-74, V H 3-73, V H 3-72, V H 2-70, V H 1-69, V H 3-66, V H 3-64, V H 4-61, V H 4-59, V H 1-58, V H 3-53, V H 5-51, V H 3-49, V H 3-48, V H 1-46, V H 1-45, V H 3-43, V H 4-39, V H 4-34, V H 3-33, V H 4-31, V H 3-30, V H 4-28, V H 2-26, V H 1-24, V H 3-23, V H 3-21, V H 3-20, V H 1-18, V H 3-15, V H 3-13, V H 3-11, V H 3-9, V H 1-8, V H 3-7, V H 2-5, V H 7-4-1, V H 4-4, V H 1-3, V H 1-2, V H 6-1, or any combination thereof. In some embodiments, one or more human V H Gene segments include V H 3-74, V H 3-73, V H 3-72, V H 2-70, V H 1-69, V H 3-66, V H 3-64, V H 4-61, V H 4-59, V H 1-58, V H 3-53, V H 5-51, V H 3-49, V H3-48, V H 1-46, V H 1-45, V H 3-43, V H 4-39, V H 4-34, V H 3-33, V H 4-31, V H 3-30, V H 4-28, V H 2-26, V H 1-24, V H 3-23, V H 3-21, V H 3-20, V H 1-18, V H 3-15, V H 3-13, V H 3-11, V H 3-9, V H 1-8, V H 3-7, V H 2-5, V H 7-4-1, V H 4-4, V H 1-3, V H 1-2 and V H 6-1. In some embodiments, one or more human D H Gene segments include D H 1-1, D H 2-2, D H 3-3, D H 4-4, D H 5-5, D H 6-6, D H 1-7, D H 2-8, D H 3-9, D H 3-10, D H 5-12, D H 6-13, D H 2-15, D H 3-16, D H 4-17, D H 6-19, D H 1-20, D H 2-21, D H 3-22, D H 6-25, D H 1-26, D H 7-27, or any combination thereof. In some embodiments, one or more human D H Gene segments include D H 1-1, D H 2-2, D H 3-3, D H 4-4, D H 5-5, D H 6-6, D H 1-7, D H 2-8, D H 3-9, D H 3-10, D H 5-12, D H 6-13, D H 2-15, D H 3-16, D H 4-17, D H 6-19, D H 1-20, D H 2-21, D H 3-22, D H 6-25, D H 1-26 and D H 7-27. In some embodiments, one or more human J H Gene segments include J H 1. J H 2. J H 3. J H 4. J H 5. J H 6, or any combination thereof. In some embodiments, one or more human J H Gene segments include J H 1. J H 2. J H 3. J H 4. J H 5 and J H 6. In some embodiments, the engineered endogenous immunoglobulin heavy chain locus comprises one or more human V Hnon-coding sequences, each of which is adjacent to the one or more human V H At least one of the gene segments, wherein the one or more V H Each of the noncoding sequences is a naturally occurring human V H In some embodiments, the one or more human V H Each of the non-coding sequences is or includes an intron. In some embodiments, the engineered endogenous immunoglobulin heavy chain locus includes one or more human D H non-coding sequences, each of which is adjacent to the one or more human D H At least one of the gene segments, wherein the one or more D H Each of the noncoding sequences is a naturally occurring human D sequence adjacent to an endogenous human immunoglobulin heavy chain locus. H In some embodiments, the one or more human D H Each of the non-coding sequences is or includes an intron. In some embodiments, the engineered endogenous immunoglobulin heavy chain locus includes one or more human J H non-coding sequences, each of which is adjacent to one or more human J H At least one of the gene segments, wherein the one or more J H Each of the non-coding sequences is a naturally occurring human J H In some embodiments, the one or more human J H Each of the non-coding sequences is or includes an intron. In some embodiments, the rodents described herein are homozygous for the engineered endogenous immunoglobulin heavy chain loci. In some embodiments, the rodent immunoglobulin heavy chain constant region is an endogenous rodent immunoglobulin heavy chain constant region. In some embodiments, the endogenous Vλ gene segment, the endogenous Jλ gene segment, and the endogenous Cλ gene are all or partially deleted. In some embodiments, the rodents described herein do not detectably express endogenous immunoglobulin λ light chain variable domains. In some embodiments, the rodents described herein do not detectably express endogenous immunoglobulin κ light chain variable domains. In some embodiments, the modified endogenous immunoglobulin heavy chain locus lacks a functional endogenous rodent Adam6 gene. In some embodiments, the rodent germline genome comprises one or more nucleotide sequences encoding one or more rodent ADAM6 polypeptides, functional orthologs, functional homologs, or functional fragments thereof. In some embodiments, one or more rodent ADAM6 polypeptides, functional orthologs, functional homologs, or functional fragments thereof are expressed (e.g., in cells of the male reproductive system, such as testicular cells). In some embodiments, one or more nucleotide sequences encoding one or more rodent ADAM6 polypeptides, functional orthologs, functional homologs, or functional fragments thereof are included on the same chromosome as the modified endogenous immunoglobulin heavy chain locus. In some embodiments, one or more nucleotide sequences encoding one or more rodent ADAM6 polypeptides, functional orthologs, functional homologs, or functional fragments thereof are included in the modified endogenous immunoglobulin heavy chain locus. In some embodiments, one or more nucleotide sequences encoding one or more rodent ADAM6 polypeptides, functional orthologs, functional homologs, or functional fragments thereof are between the first human V H Gene fragment and second human V H In some embodiments, the first human V H The gene segment is V H 1-2, and the second human V H The gene segment is V H6-1. In some embodiments, one or more nucleotide sequences encoding one or more rodent ADAM6 polypeptides, their functional orthologs, their functional homologs, or their functional fragments are located at the human Adam6 pseudogene. In some embodiments, one or more nucleotide sequences encoding one or more rodent ADAM6 polypeptides, their functional orthologs, their functional homologs, or their functional fragments replace the human Adam6 pseudogene. In some embodiments, one or more nucleotide sequences encoding one or more rodent ADAM6 polypeptides, their functional orthologs, their functional homologs, or their functional fragments are located between a human V H Gene fragment and human D H between gene fragments. In some embodiments, the rodents described herein comprise a population of B cells expressing antibodies comprising immunoglobulin lambda light chains, each of which comprises a human immunoglobulin lambda light chain variable domain. In some embodiments, the human immunoglobulin lambda light chain variable domain is encoded by a rearranged human immunoglobulin lambda light chain variable region sequence comprising (i) one of one or more human Vλ gene segments, or somatically hypermutated variants thereof, and (ii) one of one or more human Jλ gene segments, or somatically hypermutated variants thereof. In some embodiments, the rodents described herein comprise a population of B cells expressing antibodies comprising immunoglobulin heavy chains, each of which comprises a human immunoglobulin heavy chain variable domain. In some embodiments, the human immunoglobulin heavy chain variable domain is encoded by a rearranged human immunoglobulin heavy chain variable region sequence comprising (i) one of one or more human VH gene segments, or somatically hypermutated variants thereof, (ii) one of one or more human DH gene segments, or somatically hypermutated variants thereof, and (ii) one of one or more human JH gene segments, or somatically hypermutated variants thereof. In some embodiments, the rodents described herein are immunized against an antigen comprising one or more epitopes to produce a population of B cells. In some embodiments, the rodents produce a population of B cells that express antibodies that bind (e.g., specifically bind) to one or more epitopes of the antigen of interest. In some embodiments, the antibodies expressed by the population of B cells produced in response to the antigen include a heavy chain having a human heavy chain variable domain encoded by a human heavy chain variable region sequence, and / or a lambda light chain having a human lambda light chain variable domain encoded by a human lambda light chain variable region sequence as described herein. In some embodiments, the antibodies expressed by the population of B cells produced in response to the antigen include a heavy chain having a human heavy chain variable domain encoded by a human heavy chain variable region sequence, and / or a kappa light chain having a human kappa light chain variable domain encoded by a human kappa light chain variable region sequence as described herein. In some embodiments, the rodent produces a population of B cells that express antibodies that bind to one or more epitopes of an antigen of interest, wherein the antibodies expressed by the population of B cells produced in response to the antigen include: (i) a heavy chain having a human heavy chain variable domain encoded by a human heavy chain variable region sequence, (ii) a lambda light chain having a lambda light chain variable domain encoded by a human lambda light chain variable region sequence as described herein, (iii) a kappa light chain having a human kappa light chain variable domain encoded by a human kappa light chain variable region sequence as described herein, or (iv) any combination thereof. In some embodiments, the human heavy chain variable region sequences, human lambda light chain variable region sequences, and / or human kappa light chain variable region sequences described herein are somatically hypermutated. In some embodiments, at least about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% of the B cell lineage of a population of B cells generated in response to an antigen comprises a human heavy chain variable region sequence, a lambda light chain variable region sequence, and / or a somatically hypermutated kappa light chain variable region sequence. In some embodiments, the rodent described herein is a mouse or a rat. In some embodiments, cells and / or tissues (e.g., isolated cells and / or tissues) from rodents are described herein. In some embodiments, the cells and tissues provided include, for example, lymphoid tissue, spleen cells, B cells, stem cells, and / or germ cells. In some embodiments, the cell lines provided are separated. In some embodiments, the isolated cells are or include primitive B cells, precursor B cells, immature B cells, mature initial B cells, activated B cells, memory B cells, B lineage lymphocytes, and / or plasma cells. In some embodiments, the isolated cells include stem cells (e.g., embryonic stem cells), and / or germ cells (e.g., sperm, oocytes). In some embodiments, the present disclosure provides isolated rodent cells whose germline genome comprises: Modified endogenous immunoglobulin kappa light chain locus, including: (a) one or more human Vλ gene segments, (b) one or more human Jλ gene segments, and (c) Cλ gene, The one or more human Vλ gene segments and the one or more human Jλ gene segments are operably linked to the Cλ gene. In some embodiments, the isolated rodent cells described herein lack a rodent CK gene at an engineered endogenous immunoglobulin κ locus. In some embodiments, the isolated rodent cells described herein are rodent embryonic stem (ES) cells. In some embodiments, the present disclosure provides rodent embryos produced from the rodent ES cells described herein. In some embodiments, the present disclosure provides immortalized cells produced from the isolated rodent cells described herein. In some embodiments, the present invention provides a method for producing a rodent comprising an engineered endogenous immunoglobulin kappa light chain locus in its germline genome, the method comprising the steps of: (a) introducing one or more DNA segments into the germline genome of a rodent ES cell, wherein the one or more DNA segments comprise: (i) one or more human Vλ gene segments, (ii) one or more human Jλ gene segments, and (iii) one or more Cλ genes, wherein the one or more human Vλ gene segments, the one or more human Jλ gene segments, and the one or more Cλ genes are introduced into the endogenous immunoglobulin kappa light chain locus in the germline genome of the rodent ES cell, and wherein the one or more human Vλ gene segments, the one or more human Jλ gene segments, and the one or more Cλ genes are operably linked; and (b) Rodents were generated using the rodent ES cells generated in (a). In some embodiments, a method for preparing a rodent comprising an engineered endogenous immunoglobulin κ light chain locus in its germline genome comprises the step of introducing a κ light chain non-coding sequence into the germline genome of a rodent ES cell such that the κ light chain non-coding sequence is interposed between one or more human Vλ gene segments and one or more human Jλ gene segments in the rodent ES cell germline genome. In some embodiments, the present invention provides a method for producing a rodent comprising an engineered endogenous immunoglobulin kappa light chain locus in its germline genome, the method comprising the steps of: The endogenous immunoglobulin kappa light chain locus in the germline genome is engineered to include: (a) one or more human Vλ gene segments, (b) one or more human Jλ gene segments, and (c) one or more Cλ genes, wherein the one or more human Vλ gene segments and the one or more human Jλ gene segments are operatively linked to the one or more Cλ genes, and wherein the one or more Cλ genes are inserted to replace the rodent CK gene at the endogenous immunoglobulin κ locus. In some embodiments, the Cλ gene replaces the rodent CK gene at the endogenous immunoglobulin κ locus. In some embodiments, the one or more human Vλ gene segments include Vλ5-52, Vλ1-51, Vλ9-49, Vλ1-47, Vλ7-46, Vλ5-45, Vλ1-44, Vλ7-43, Vλ1-40, Vλ5-39, Vλ5-37, Vλ1-36, Vλ3-27, Vλ3-25, Vλ2-23, Vλ3-22, Vλ3-21, Vλ3-19, Vλ2-18, Vλ3-16, Vλ2-14, Vλ3-12, Vλ2-11, Vλ3-10, Vλ3-9, Vλ2-8, Vλ4-3, Vλ3-1, or any combination thereof. In some embodiments, a plurality of human Vλ gene segments include Vλ5-52, Vλ1-51, Vλ9-49, Vλ1-47, Vλ7-46, Vλ5-45, Vλ1-44, Vλ7-43, Vλ1-40, Vλ3-27, Vλ3-25, Vλ2-23, Vλ3-22, Vλ3-21, Vλ3-19, Vλ2-18, Vλ3-16, Vλ2-14, Vλ3-12, Vλ2-11, Vλ3-10, Vλ3-9, Vλ2-8, Vλ4-3, and Vλ3-1. In some embodiments, a plurality of human Vλ gene segments include Vλ5-52, Vλ1-51, Vλ9-49, Vλ1-47, Vλ7-46, Vλ5-45, Vλ1-44, Vλ7-43, Vλ1-40, Vλ5-39, Vλ5-37, Vλ1-36, Vλ3-27, Vλ3-25, Vλ2-23, Vλ3-22, Vλ3-21, Vλ3-19, Vλ2-18, Vλ3-16, Vλ2-14, Vλ3-12, Vλ2-11, Vλ3-10, Vλ3-9, Vλ2-8, Vλ4-3, and Vλ3-1. In some embodiments, the one or more human Jλ gene segments include Jλ1, Jλ2, Jλ3, Jλ6, Jλ7, or any combination thereof. In some embodiments, the one or more human Jλ gene segments include Jλ1, Jλ2, Jλ3, Jλ6, and Jλ7. In some embodiments, the modified endogenous immunoglobulin κ light chain locus comprises one or more human νλ non-coding sequences, each of which is adjacent to at least one of the one or more human νλ gene segments, wherein the one or more human νλ non-coding sequences naturally occur adjacent to the human νλ gene segment of the endogenous human immunoglobulin λ light chain locus. In some embodiments, each of the one or more human νλ non-coding sequences is or comprises an intron. In some embodiments, the modified endogenous immunoglobulin κ light chain locus comprises one or more human νλ non-coding sequences, each of which is adjacent to at least one of the one or more human νλ gene segments, wherein the one or more human νλ non-coding sequences naturally occur adjacent to the human νλ gene segment of the endogenous human immunoglobulin λ light chain locus. In some embodiments, each of the one or more human νλ non-coding sequences is or comprises an intron. In some embodiments, the modified endogenous immunoglobulin κ light chain locus comprises one or more human Jκ non-coding sequences, each of which is adjacent to at least one of the one or more human Jλ gene segments, wherein the one or more human Jκ non-coding sequences naturally occur adjacent to the human Jκ gene segment of the endogenous human immunoglobulin κ light chain locus. In some embodiments, each of the one or more human Jκ non-coding sequences is or comprises an intron. In some embodiments, the Cλ gene is or comprises a rodent Cλ gene. In some embodiments, the rodent Cλ gene has a sequence that is at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% identical to a mouse Cλ1, mouse Cλ2, or mouse Cλ3 gene. In some embodiments, the rodent Cλ gene is or comprises a mouse Cλ1 gene. In some embodiments, the rodent Cλ gene is or comprises a rat Cλ gene. In some embodiments, the rat Cλ gene has a sequence that is at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% identical to a rat Cλ1, rat Cλ2, rat Cλ3, or rat Cλ4 gene. In some embodiments, one or more DNA segments comprise at least one selection marker. In some embodiments, one or more DNA segments comprise at least one site-specific recombination site. In some embodiments, a rodent's germline genome comprises: An engineered endogenous immunoglobulin heavy chain locus comprising: (a) One or more human V H gene fragments, (b) one or more human D H gene fragments, and (c) one or more human J H gene fragments, wherein the one or more human V H gene fragments, the one or more human D H Gene fragments, and the one or more human J H The gene segment is operably linked to a rodent immunoglobulin heavy chain constant region. In some embodiments, the step of engineering the endogenous immunoglobulin kappa light chain locus in the germline genome is performed in rodent ES cells, wherein the germline genome comprises an engineered endogenous immunoglobulin heavy chain locus comprising one or more human V H Gene fragments, one or more human D H gene fragments, and one or more human J H The gene segment is operably linked to a rodent immunoglobulin heavy chain constant region. In some embodiments, the engineered endogenous immunoglobulin heavy chain locus comprises one or more human V H non-coding sequences, each of which is adjacent to one or more human V H At least one of the gene segments, wherein the one or more human V H Each of the noncoding sequences naturally occurs in the human V adjacent to the endogenous human immunoglobulin heavy chain locus. H In some embodiments, the one or more human V H Each of the non-coding sequences is or includes an intron. In some embodiments, the engineered endogenous immunoglobulin heavy chain locus includes one or more human D H non-coding sequences, each of which is adjacent to one or more human D H At least one of the gene segments, wherein the one or more D H Each of the noncoding sequences naturally occurs in human DNA adjacent to the endogenous human immunoglobulin heavy chain locus. H In some embodiments, the one or more human D H Each of the non-coding sequences is or includes an intron. In some embodiments, the engineered endogenous immunoglobulin heavy chain locus includes one or more human J H non-coding sequences, each of which is adjacent to the one or more human J H At least one of the gene segments, wherein the one or more J H Each of the non-coding sequences naturally occurs in the human J adjacent to the endogenous human immunoglobulin heavy chain locus. H In some embodiments, the one or more human J H Each of the non-coding sequences is or includes an intron. In some embodiments, the present invention provides a method for producing antibodies in a rodent, the method comprising the steps of: (i) immunizing a rodent with an antigen of interest, The rodent has a germline genome comprising: An engineered endogenous immunoglobulin kappa light chain locus comprising: (a) one or more human Vλ gene segments, (b) one or more human Jλ gene segments, and (c) one or more Cλ genes, wherein the one or more human Vλ gene segments and the one or more human Jλ gene segments are operably linked to the Cλ gene, and wherein the one or more Cλ genes are located at a rodent Cκ gene of the modified endogenous immunoglobulin κ light chain locus; maintaining the rodent under conditions sufficient for the rodent to mount an immune response to the antigen of interest; and Antibodies that bind to the antigen of interest are recovered from the rodent, rodent cell, or cell derived from the rodent cell. In some embodiments, in response to the immunization step, the rodent produces B cells that express antibodies that bind to the antigen of interest. In some embodiments, the antibodies expressed by the B cells include a heavy chain having a human heavy chain variable domain encoded by a human heavy chain variable region sequence, and / or a lambda light chain having a human lambda light chain variable domain encoded by a human lambda light chain variable region sequence, as described herein. In some embodiments, the antibodies expressed by the B cells include (i) a heavy chain having a human heavy chain variable domain encoded by a human heavy chain variable region sequence, (ii) a lambda light chain having a human lambda light chain variable domain encoded by a human lambda light chain variable region sequence, (iii) a kappa light chain having a human kappa light chain variable domain encoded by a human kappa light chain variable region sequence, or (iv) any combination thereof. In some embodiments, in response to the immunization step, the rodent produces B cells that express antibodies that bind to the antigen of interest. In some embodiments, the antibodies expressed by the population of B cells produced in response to the antigen include a heavy chain having a human heavy chain variable domain encoded by a human heavy chain variable region sequence, and / or a lambda light chain having a human lambda light chain variable domain encoded by a human lambda light chain variable region sequence as described herein. In some embodiments, the antibodies expressed by the population of B cells produced in response to the antigen include (i) a heavy chain having a human heavy chain variable domain encoded by a human heavy chain variable region sequence, (ii) a lambda light chain having a human lambda light chain variable domain encoded by a human lambda light chain variable region sequence as described herein, (iii) a kappa light chain having a human kappa light chain variable domain encoded by a human kappa light chain variable region sequence as described herein, or (iv) any combination thereof. In some embodiments, in response to the immunization step, the rodent produces a population of B cells that express antibodies that bind to one or more epitopes of the antigen of interest, wherein the antibodies expressed by the population of B cells produced in response to an antigen include: (i) heavy chains having human heavy chain variable domains encoded by human heavy chain variable region sequences, (ii) lambda light chains having lambda light chain variable domains encoded by human lambda light chain variable region sequences as described herein, (iii) kappa light chains having human kappa light chain variable domains encoded by human kappa light chain variable region sequences as described herein, or (iv) any combination thereof. In some embodiments, the human heavy chain variable region sequences, human lambda light chain variable region sequences, and / or human kappa light chain variable region sequences described herein are somatically hypermutated. In some embodiments, at least about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% of the B cell lineage of a population of B cells generated in response to an antigen comprises a human heavy chain variable region sequence, a lambda light chain variable region sequence, and / or a somatically hypermutated kappa light chain variable region sequence. In some embodiments, antibodies that bind to an antigen of interest are isolated, recovered, or identified from rodent B cells. In some embodiments, antibodies that bind to an antigen of interest are isolated, recovered, or identified from a fusion tumor prepared from rodent B cells. In some embodiments, the antigen includes one or more epitopes, and the antibody that binds to the antigen of interest binds to one of the one or more epitopes. In some embodiments, the Cλ gene is or comprises a rodent Cλ gene. In some embodiments, the rodent Cλ gene has a sequence that is at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% identical to a mouse Cλ1, mouse Cλ2, or mouse Cλ3 gene. In some embodiments, the rodent Cλ gene is or comprises a mouse Cλ1 gene. In some embodiments, the rodent Cλ gene is or comprises a rat Cλ gene. In some embodiments, the rat Cλ gene has a sequence that is at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% identical to a rat Cλ1, rat Cλ2, rat Cλ3, or rat Cλ4 gene. In some embodiments, the one or more human Vλ gene segments comprise Vλ5-52, Vλ1-51, Vλ9-49, Vλ1-47, Vλ7-46, Vλ5-45, Vλ1-44, Vλ7-43, Vλ1-40, Vλ5-39, Vλ5-37, Vλ1-36, Vλ3-27, Vλ3-25, Vλ2-23, Vλ3-22, Vλ3-21, Vλ3-19, Vλ2-18, Vλ3-16, Vλ2-14, Vλ3-12, Vλ2-11, Vλ3-10, Vλ3-9, Vλ2-8, Vλ4-3, Vλ3-1, or any combination thereof. In some embodiments, the one or more human Vλ gene segments include Vλ5-52, Vλ1-51, Vλ9-49, Vλ1-47, Vλ7-46, Vλ5-45, Vλ1-44, Vλ7-43, Vλ1-40, Vλ3-27, Vλ3-25, Vλ2-23, Vλ3-22, Vλ3-21, Vλ3-19, Vλ2-18, Vλ3-16, Vλ2-14, Vλ3-12, Vλ2-11, Vλ3-10, Vλ3-9, Vλ2-8, Vλ4-3, and Vλ3-1. In some embodiments, the one or more human Vλ gene segments include Vλ5-52, Vλ1-51, Vλ9-49, Vλ1-47, Vλ7-46, Vλ5-45, Vλ1-44, Vλ7-43, Vλ1-40, Vλ5-39, Vλ5-37, Vλ1-36, Vλ3-27, Vλ3-25, Vλ2-23, Vλ3-22, Vλ3-21, Vλ3-19, Vλ2-18, Vλ3-16, Vλ2-14, Vλ3-12, Vλ2-11, Vλ3-10, Vλ3-9, Vλ2-8, Vλ4-3, and Vλ3-1. In some embodiments, the one or more human Jλ gene segments comprise Jλ1, Jλ2, Jλ3, Jλ6, Jλ7, or any combination thereof. In some embodiments, the one or more human Jλ gene segments comprise Jλ1, Jλ2, Jλ3, Jλ6, and Jλ7. In some embodiments, the engineered endogenous immunoglobulin κ light chain locus comprises one or more human νλ non-coding sequences, wherein each of the one or more human νλ non-coding sequences is adjacent to νλ5-52, νλ1-51, νλ9-49, νλ1-47, νλ7-46, νλ5-45, νλ1-44, νλ7-43, νλ1-40, νλ5-39, νλ5-37, νλ1-36, νλ3-27, νλ3-25, νλ2-23, νλ3-22, νλ3-21, νλ3-19, νλ2-18, νλ3-16, νλ2-14, νλ3-12, νλ2-11, νλ3-10, νλ3-9, Vλ2-8, Vλ4-3 or Vλ3-1, and wherein each of the one or more human Vλ non-coding sequences naturally occurs adjacent to an endogenous human immunoglobulin lambda light chain locus Vλ5-52, Vλ1-51, Vλ9-49, Vλ1-47, Vλ7-46, Vλ5-45, Vλ1-44, Vλ7-43, Vλ1-40, Vλ5-39, Vλ5-37, Vλ1-36, Vλ3-27, Vλ3-25, Vλ2-23, Vλ3-22, Vλ3-21, Vλ3-19, Vλ2-18, Vλ3-16, Vλ2-14, Vλ3-12, Vλ2-11, Vλ3-10, Vλ3-9, Vλ2-8, Vλ4-3 or Vλ3-1. In some embodiments, the engineered endogenous immunoglobulin κ light chain locus comprises one or more human Jλ non-coding sequences, wherein each of the one or more human Jλ non-coding sequences is adjacent to Jλ1, Jλ2, Jλ3, Jλ6, or Jλ7 of the engineered endogenous immunoglobulin κ light chain locus, and wherein each of the one or more human Jλ non-coding sequences naturally occurs adjacent to Jλ1, Jλ2, Jλ3, Jλ6, or Jλ7 of the endogenous human immunoglobulin λ light chain locus. In some embodiments, the engineered endogenous immunoglobulin κ light chain locus comprises one or more human Jκ non-coding sequences, wherein each of the one or more human Jκ non-coding sequences is adjacent to Jλ1, Jλ2, Jλ3, Jλ6, or Jλ7 of the engineered endogenous human immunoglobulin κ light chain locus, and wherein each of the one or more human Jκ non-coding sequences naturally occurs adjacent to Jκ1, Jκ2, Jκ3, Jκ4, or Jκ5 of the endogenous human immunoglobulin κ light chain locus. In some embodiments, the rodent has a germline genome comprising an engineered endogenous immunoglobulin heavy chain locus comprising: (a) One or more human V H gene fragments, (b) one or more human D H gene fragments, and (c) one or more human J H gene fragments, wherein the one or more human V H gene fragments, the one or more human D H Gene fragments, and the one or more human J H The gene segment is operably linked to a rodent immunoglobulin heavy chain constant region. In some embodiments, one or more human V H The gene segment contains V H 3-74, V H 3-73, V H 3-72, V H 2-70, V H 1-69, V H 3-66, V H 3-64, V H 4-61, V H 4-59, V H 1-58, V H 3-53, V H 5-51, V H 3-49, V H 3-48, V H 1-46, V H 1-45, V H 3-43, V H 4-39, V H 4-34, V H 3-33, V H 4-31, V H 3-30, V H 4-28, V H 2-26, V H 1-24, V H 3-23, V H 3-21, V H 3-20, V H 1-18, V H 3-15, V H 3-13, V H 3-11, V H 3-9, V H 1-8, V H 3-7, V H 2-5, V H 7-4-1, V H 4-4, V H 1-3, V H 1-2, V H 6-1, or any combination thereof. In some embodiments, one or more human V H The gene segment contains V H 3-74, V H 3-73, V H 3-72, V H 2-70, V H 1-69, V H 3-66, V H 3-64, V H 4-61, V H 4-59、V H 1-58、V H 3-53、V H 5-51、V H 3-49、V H 3-48、V H 1-46、V H 1-45、V H 3-43、V H 4-39、V H 4-34、V H 3-33、V H 4-31、V H 3-30、V H 4-28、V H 2-26、V H 1-24、V H 3-23、V H 3-21、V H 3-20、V H 1-18、V H 3-15、V H 3-13、V H 3-11、V H 3-9、V H 1-8、V H 3-7、V H 2-5、V H 7-4-1、V H 4-4、V H1-3, V H 1-2 and V H 6-1. In some embodiments, one or more human D H The gene fragment contains D H 1-1, D H 2-2, D H 3-3, D H 4-4, D H 5-5, D H 6-6, D H 1-7, D H 2-8, D H 3-9, D H 3-10, D H 5-12, D H 6-13, D H 2-15, D H 3-16, D H 4-17, D H 6-19, D H 1-20, D H 2-21, D H 3-22, D H 6-25, D H 1-26, D H 7-27, or any combination thereof. In some embodiments, one or more human D H The gene fragment contains D H 1-1, D H 2-2, D H 3-3, D H 4-4, D H 5-5, D H 6-6, D H 1-7, D H 2-8, D H 3-9, D H 3-10, D H 5-12, D H 6-13, D H 2-15, D H 3-16, D H 4-17, D H 6-19, D H 1-20, D H 2-21, D H 3-22, D H 6-25, D H 1-26 and D H 7-27. In some embodiments, one or more human J H The gene fragment contains J H 1. J H 2. J H 3. J H 4. J H 5. J H 6, or any combination thereof. In some embodiments, one or more human J H The gene fragment contains J H 1. J H 2. J H3. J H 4. J H 5 and J H 6. In some embodiments, an engineered endogenous immunoglobulin heavy chain locus comprises one or more human V H non-coding sequence, wherein the one or more human V H Each of the non-coding sequences is adjacent to the V H 3-74, V H 3-73, V H 3-72, V H 2-70, V H 1-69, V H 3-66, V H 3-64, V H 4-61, V H 4-59, V H 1-58, V H 3-53, V H 5-51, V H 3-49, V H 3-48, V H 1-46, V H 1-45, V H 3-43, V H 4-39, V H 4-34, V H 3-33, V H 4-31, V H 3-30, V H4-28, V H 2-26, V H 1-24, V H 3-23, V H 3-21, V H 3-20, V H 1-18, V H 3-15, V H 3-13, V H 3-11, V H 3-9, V H 1-8, V H 3-7, V H 2-5, V H 7-4-1, V H 4-4, V H 1-3, V H 1-2 or V H 6-1, and wherein the one or more human beings V H Each of the non-coding sequences naturally occurs near an endogenous human immunoglobulin heavy chain locus V H 3-74, V H 3-73, V H 3-72, V H 2-70, V H 1-69, V H 3-66, V H 3-64, V H 4-61, V H 4-59, V H 1-58, V H 3 - 53, V H 5 - 51, V H 3 - 49, V H 3 - 48, V H 1 - 46, V H 1 - 45, V H 3 - 43, V H 4 - 39, V H 4 - 34, V H 3 - 33, V H 4 - 31, V H 3 - 30, V H 4 - 28, V H 2 - 26, V H 1 - 24, V H 3 - 23, V H 3 - 21, V H 3 - 20, V H 1 - 18, V H 3 - 15, V H 3 - 13, V H 3 - 11, V H 3 - 9, V H 1 - 8, V H 3 - 7, V H 2 - 5, V H 7 - 4 - 1, V H 4 - 4, V H 1 - 3, V H 1 - 2 or V H 6-1. In some embodiments, the engineered endogenous immunoglobulin heavy chain locus comprises one or more human D H non-coding sequence, wherein the one or more human D H Each of the non-coding sequences is adjacent to the modified endogenous immunoglobulin heavy chain locus. H 1-1, D H 2-2, D H 3-3, D H 4-4, D H 5-5, D H 6-6, D H 1-7, D H 2-8, D H 3-9, D H 3-10, D H 5-12, D H 6-13, D H 2-15, D H 3-16, D H 4-17, D H 6-19, D H 1-20, D H 2-21, D H 3-22, D H 6-25, D H 1-26, or D H 7-27, and wherein the one or more human D H Each of the non-coding sequences naturally occurs adjacent to an endogenous human immunoglobulin heavy chain locus. H 1-1, D H 2-2, D H 3-3, D H 4-4, D H 5-5, D H 6-6, D H 1-7, D H 2-8, D H 3-9, D H 3-10, D H 5-12, D H 6-13, D H 2-15, D H 3-16, D H 4-17, D H 6-19, D H 1-20, D H 2-21, D H 3-22, D H 6-25, D H 1-26, or D H 7-27. In some embodiments, the modified endogenous immunoglobulin heavy chain locus includes one or more human J H Non-coding sequence, wherein the one or more human J H Each of the non-coding sequences is adjacent to the modified endogenous immunoglobulin heavy chain locus H 1. J H 2. J H 3. J H 4. J H 5 or J H 6, and one or more human beings J H Each of the non-coding sequences naturally occurs adjacent to the endogenous human immunoglobulin heavy chain locus. H 1. J H 2. J H 3. J H 4. J H 5, or J H 6. In some embodiments, the recovered rodent cells are B cells. In some embodiments, the cells derived from rodent cells are hybridomas. In some embodiments, the nucleotide sequence encoding the human heavy chain variable region sequence, the human lambda light chain variable region sequence, and / or the human kappa light chain variable region sequence is obtained from a B cell. In some embodiments, the modified endogenous immunoglobulin heavy chain locus lacks a functional endogenous rodent Adam6 gene. In some embodiments, the rodent germline genome comprises one or more nucleotide sequences encoding one or more rodent ADAM6 polypeptides, functional orthologs, functional homologs, or functional fragments thereof. In some embodiments, one or more rodent ADAM6 polypeptides, functional orthologs, functional homologs, or functional fragments thereof are expressed (e.g., in male reproductive system cells, such as testicular cells). In some embodiments, one or more nucleotide sequences encoding one or more rodent ADAM6 polypeptides, functional orthologs, functional homologs, or functional fragments thereof are included on the same chromosome as the modified endogenous immunoglobulin heavy chain locus. In some embodiments, one or more nucleotide sequences encoding one or more rodent ADAM6 polypeptides, functional orthologs, functional homologs, or functional fragments thereof are included in the modified endogenous immunoglobulin heavy chain locus. In some embodiments, one or more nucleotide sequences encoding one or more rodent ADAM6 polypeptides, functional orthologs, functional homologs, or functional fragments thereof are between the first human V H Gene fragment and second human V H In some embodiments, the first human V H The gene segment is V H 1-2, and the second human V H The gene segment is V H 6-1. In some embodiments, one or more nucleotide sequences encoding one or more rodent ADAM6 polypeptides, their functional orthologs, their functional homologs, or their functional fragments are located at the human Adam6 pseudogene. In some embodiments, one or more nucleotide sequences encoding one or more rodent ADAM6 polypeptides, their functional orthologs, their functional homologs, or their functional fragments replace the human Adam6 pseudogene. In some embodiments, one or more nucleotide sequences encoding one or more rodent ADAM6 polypeptides, their functional orthologs, their functional homologs, or their functional fragments are located between a human V H Gene fragment and human D H between gene fragments. In some embodiments, the rodent is a mouse or a rat. In some embodiments, the present invention provides a rodent whose germline genome comprises a homozygous engineered endogenous immunoglobulin kappa light chain locus comprising: (i) one or more human Vλ gene segments, wherein the one or more human Vλ gene segments comprise Vλ5-52, Vλ1-51, Vλ9-49, Vλ1-47, Vλ7-46, Vλ5-45, Vλ1-44, Vλ7-43, Vλ1-40, Vλ5-39, Vλ5-37, Vλ1-36, Vλ3-27, Vλ3-25, Vλ2-23, Vλ3-22, Vλ3-21, Vλ3-19, Vλ2-18, Vλ3-16, Vλ2-14, Vλ3-12, Vλ2-11, Vλ3-10, Vλ3-9, Vλ2-8, Vλ4-3, Vλ3-1, or any combination thereof, (ii) one or more human Jλ gene segments, wherein the one or more human Jλ gene segments comprise Jλ1, Jλ2, Jλ3, Jλ6, Jλ7, or any combination thereof, and (iii) rodent Cλ gene; wherein the one or more human Vλ gene segments, the one or more human Jλ gene segments and the rodent Cλ gene are operably linked to each other, wherein the rodent Cλ gene is located at the rodent Cκ gene of the endogenous immunoglobulin κ light chain locus, The modified endogenous immunoglobulin κ light chain locus comprises: (a) one or more human non-coding sequences, wherein each of the one or more human Vλ non-coding sequences is adjacent to Vλ5-52, Vλ1-51, Vλ9-49, Vλ1-47, Vλ7-46, Vλ5-45, Vλ1-44, Vλ7-43, Vλ1-40, Vλ5-39, Vλ5-37, Vλ1-36, Vλ3-27, Vλ3-25, Vλ2-23, Vλ3-22, Vλ3-21, Vλ3-19, Vλ2-18, Vλ3-16, Vλ2-14, Vλ3-12, Vλ2-11, Vλ3-10, Vλ3-9, Vλ2-8, Vλ4-3 or Vλ5-4 of the modified endogenous immunoglobulin κ light chain locus. wherein each of the one or more human Vλ non-coding sequences naturally occurs adjacent to an endogenous human immunoglobulin lambda light chain locus, and (b) one or more human Jκ non-coding sequences, wherein each of the one or more human Jκ non-coding sequences is adjacent to Jλ1, Jλ2, Jλ3, Jλ6, or Jλ7 of the modified endogenous immunoglobulin κ light chain locus, and wherein each of the one or more human Jκ non-coding sequences naturally occurs adjacent to Jκ1, Jκ2, Jκ3, Jκ4, or Jκ5 of the endogenous human immunoglobulin κ light chain locus, and The immunoglobulin κ light chain locus includes a human κ light chain non-coding sequence, which is between the one or more human Vλ gene segments and the one or more human Jλ gene segments, and has a sequence that naturally occurs between the human Vκ4-1 gene segment and the human Jκ1 gene segment of the endogenous human immunoglobulin κ light chain locus. In some embodiments, the rodent Cλ gene is a mouse Cλ1 gene. In some embodiments, the engineered endogenous immunoglobulin kappa light chain locus includes the rodent immunoglobulin kappa light chain enhancer Eκ i and Eκ3′. In some embodiments, the endogenous immunoglobulin κ light chain locus is modified to include deletions of one or more rodent Vκ gene segments and / or one or more Jκ gene segments. In some embodiments, the endogenous immunoglobulin κ light chain locus is modified to include deletions of all functional rodent Vκ and / or Jκ gene segments. In some embodiments, the present invention provides a rodent having a germline genome comprising: (a) a homozygous endogenous immunoglobulin heavy chain locus comprising one or more human V H Gene fragments, one or more human D H gene fragments, and one or more human J H A gene segment operatively linked to one or more endogenous immunoglobulin heavy chain constant region genes such that the rodent can express immunoglobulin heavy chains, each heavy chain comprising a human heavy chain variable domain sequence and a rodent heavy chain constant domain sequence, (b) a first engineered endogenous immunoglobulin kappa light chain locus comprising one or more human Vκ gene segments and one or more Jκ gene segments operably linked to an endogenous rodent CK region gene, such that the rodent can express immunoglobulin light chains, each of which comprises a human kappa light chain variable domain sequence and a rodent kappa light chain constant domain sequence, and (c) a second engineered endogenous immunoglobulin kappa light chain locus comprising: (i) one or more human Vλ gene segments, wherein the one or more human Vλ gene segments comprise Vλ5-52, Vλ1-51, Vλ9-49, Vλ1-47, Vλ7-46, Vλ5-45, Vλ1-44, Vλ7-43, Vλ1-40, Vλ5-39, Vλ5-37, Vλ1-36, Vλ3-27, Vλ3-25, Vλ2-23, Vλ3-22, Vλ3-21, Vλ3-19, Vλ2-18, Vλ3-16, Vλ2-14, Vλ3-12, Vλ2-11, Vλ3-10, Vλ3-9, Vλ2-8, Vλ4-3, Vλ3-1, or any combination thereof, (ii) one or more human Jλ gene segments, wherein the one or more human Jλ gene segments comprise Jλ1, Jλ2, Jλ3, Jλ6, Jλ7, or any combination thereof, and (iii) rodent Cλ gene; wherein the one or more human Vλ gene segments, the one or more human Jλ gene segments, and the rodent Cλ gene are operatively linked to each other, wherein the rodent Cλ gene is located at the rodent Cκ gene of the endogenous immunoglobulin kappa light chain locus, The modified endogenous immunoglobulin κ light chain locus comprises: (a) one or more human Vλ non-coding sequences, wherein each of the one or more human Vλ non-coding sequences is adjacent to Vλ5-52, Vλ1-51, Vλ9-49, Vλ1-47, Vλ7-46, Vλ5-45, Vλ1-44, Vλ7-43, Vλ1-40, Vλ3-27, Vλ3-25, Vλ2-23, Vλ3-22, Vλ3-21, Vλ3-19, Vλ2-18, Vλ3-16, Vλ2-14, Vλ3-12, Vλ2-11, Vλ3-10, Vλ3-9, Vλ2-8, Vλ4-3 or Vλ5-52 of the modified endogenous immunoglobulin κ light chain locus. 3-1, and wherein each of the one or more human Vλ non-coding sequences naturally occurs adjacent to an endogenous human immunoglobulin lambda light chain locus, Vλ5-52, Vλ1-51, Vλ9-49, Vλ1-47, Vλ7-46, Vλ5-45, Vλ1-44, Vλ7-43, Vλ1-40, Vλ3-27, Vλ3-25, Vλ2-23, Vλ3-22, Vλ3-21, Vλ3-19, Vλ2-18, Vλ3-16, Vλ2-14, Vλ3-12, Vλ2-11, Vλ3-10, Vλ3-9, Vλ2-8, Vλ4-3 or Vλ3-1, and (b) one or more human Jκ non-coding sequences, wherein each of the one or more human Jκ non-coding sequences is adjacent to Jλ1, Jλ2, Jλ3, Jλ6, or Jλ7 of the modified endogenous immunoglobulin κ light chain locus, and wherein each of the one or more human Jκ non-coding sequences naturally occurs adjacent to Jκ1, Jκ2, Jκ3, Jκ4, or Jκ5 of the endogenous human immunoglobulin κ light chain locus, and wherein the immunoglobulin κ light chain locus comprises one or more human κ light chain non-coding sequences between one or more human Vλ gene segments and one or more human Jλ gene segments, and has a sequence that naturally occurs between the human Vκ4-1 gene segment and the human Jκ1 gene segment of an endogenous human immunoglobulin κ light chain locus; The rodent is allowed to express immunoglobulin light chains, wherein each light chain comprises a human lambda light chain variable domain sequence and a rodent lambda light chain constant domain sequence. In some embodiments, the rodents described herein comprise an inactivated endogenous immunoglobulin λ light chain locus. In some embodiments, the inactivated endogenous immunoglobulin λ light chain locus of the rodents described herein is heterozygous. In some embodiments, the inactivated endogenous immunoglobulin λ light chain locus of the rodents described herein is homozygous. In some embodiments, the rodent genome further comprises a nucleic acid sequence encoding an exogenous terminal deoxynucleotidyl transferase (TdT) operably linked to a transcriptional control unit. In some embodiments, the transcriptional control unit comprises a RAG1 transcriptional control unit, a RAG2 transcriptional control unit, an immunoglobulin heavy chain transcriptional control unit, an immunoglobulin kappa light chain transcriptional control unit, an immunoglobulin lambda light chain transcriptional control unit, or any combination thereof. In some embodiments, the nucleic acid sequence encoding the exogenous TdT is located in an immunoglobulin kappa light chain locus, an immunoglobulin lambda light chain locus, an immunoglobulin heavy chain locus, a RAG1 locus, or a RAG2 locus. In some embodiments, the TdT is human TdT. In some embodiments, the TdT is a short isoform of TdT (TdTS). In some embodiments, the rodents described herein comprise a nucleic acid sequence encoding an exogenous terminal deoxynucleotidyl transferase (TdT) operably linked to a transcriptional control unit in their germline genome and exhibit at least a 1.2-fold, at least a 1.5-fold, at least a 1.75-fold, at least a 2-fold, at least a 3-fold, at least a 4-fold, or at least a 5-fold increase in light chain junction diversity (e.g., representation of included light chain variable domains) compared to a comparable mouse (e.g., littermate) that does not comprise an exogenous terminal deoxynucleotidyl transferase (TdT) operably linked to a transcriptional control unit in its germline genome. In some embodiments, junction diversity is measured by unique CDR3 / 10,000 reads. In some embodiments, junction diversity is measured by unique CDR3 / 10,000 reads. In some embodiments, the rodents described herein include a nucleic acid sequence encoding an exogenous terminal deoxynucleotidyl transferase (TdT) operably linked to a transcriptional control unit in their germline genome, and at least 25%, at least 30%, at least 35%, at least 40%, 45%, at least 50%, at least 55%, at least 60%, at least 65% of the light chains (e.g., lambda and / or kappa light chains) produced by the rodent have non-templated incorporation. In some embodiments, the rodent described herein is a rat or a mouse. In some embodiments, the present disclosure provides an antibody prepared by a method comprising the following steps: (a) providing a rodent as described herein; (b) immunizing the rodent with an antigen of interest; (c) maintaining the rodent under conditions sufficient for the rodent to mount an immune response to the antigen of interest; and (d) recovering from the rodent, or rodent cell, or cell derived from the rodent cell, an antibody that binds to the antigen of interest, The antibody of (d) comprises a human heavy chain variable domain and a human lambda light chain variable domain. In some embodiments, the present disclosure provides an antibody prepared by a method comprising the following steps: (a) immunizing a rodent with an antigen of interest; (b) maintaining the rodent under conditions sufficient for the rodent to mount an immune response to the antigen of interest; and (c) recovering from the rodent, or rodent cell, or cell derived from the rodent cell, an antibody that binds to the antigen of interest, The antibody of (c) comprises a human heavy chain variable domain and a human lambda light chain variable domain. In some embodiments, the rodent does not detectably express endogenous immunoglobulin kappa light chain variable domains. In some embodiments, the rodent does not detectably express endogenous immunoglobulin lambda light chain variable domains. In some embodiments, the rodents described herein are immunized with an antigen comprising one or more epitopes to produce a population of B cells. In some embodiments, the rodents produce a population of B cells that express antibodies that bind (e.g., specifically bind) to one or more epitopes of the antigen of interest. In some embodiments, the antibodies expressed by the population of B cells produced in response to the antigen include a heavy chain having a human heavy chain variable domain encoded by a human heavy chain variable region sequence, and / or a lambda light chain having a human lambda light chain variable domain encoded by a human lambda light chain variable region sequence as described herein. In some embodiments, the antibodies expressed by the population of B cells produced in response to the antigen include (i) a heavy chain having a human heavy chain variable domain encoded by a human heavy chain variable region sequence, (ii) a lambda light chain having a human lambda light chain variable domain encoded by a human lambda light chain variable region sequence as described herein, (iii) a kappa light chain having a human kappa light chain variable domain encoded by a human kappa light chain variable region sequence as described herein, or (iv) any combination thereof. In some embodiments, the rodent produces a population of B cells that express antibodies that bind to one or more epitopes of an antigen of interest, wherein the antibodies expressed by the population of B cells produced in response to the antigen include: (i) a heavy chain having a human heavy chain variable domain encoded by a human heavy chain variable region sequence, (ii) a lambda light chain having a human lambda light chain variable domain encoded by a human lambda light chain variable region sequence, as described herein, and (iii) a kappa light chain having a human kappa light chain variable domain encoded by a human kappa light chain variable region sequence, as described herein. In some embodiments, the human heavy chain variable region sequences, human lambda light chain variable region sequences, and / or human kappa light chain variable region sequences described herein are somatically hypermutated. In some embodiments, at least about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% of the B cell lineage of a population of B cells generated in response to an antigen comprises a human heavy chain variable region sequence, a lambda light chain variable region sequence, and / or a somatically hypermutated kappa light chain variable region sequence. In some embodiments, the present invention provides a method for preparing an antibody, comprising: (i) expressing in a host cell a first nucleotide sequence encoding an immunoglobulin heavy chain, wherein the first nucleotide sequence comprises a human heavy chain variable region sequence; (ii) expressing in the host cell a second nucleotide sequence encoding an immunoglobulin lambda light chain, wherein the second nucleotide sequence comprises a human lambda light chain variable region sequence identified (e.g., expressed and / or isolated) from a rodent comprising the germline genome of the rodent: Modified endogenous immunoglobulin kappa light chain locus, including: (a) one or more human Vλ gene segments, (b) one or more human Jλ gene segments, and (c) one or more Cλ genes, wherein the one or more human Vλ gene segments and the one or more human Jλ gene segments are operatively linked to the one or more Cλ genes, and wherein the rodent lacks a rodent CK gene at the modified endogenous immunoglobulin κ locus; (iii) culturing the host cell so that immunoglobulin light chains and immunoglobulin heavy chains can be expressed and antibodies are formed; and (iv) obtaining the antibody from the host cell and / or host cell culture. In some embodiments, the first nucleotide sequence comprises a human heavy chain constant region. In some embodiments, the antibody is a fully human antibody. In some embodiments, the second nucleotide comprises a human lambda light chain constant region sequence. In some embodiments, the antibody is a trans chimeric antibody. In some embodiments, the first nucleotide sequence comprises a rodent heavy chain constant region. In some embodiments, the second nucleotide sequence comprises a rodent lambda light chain constant region sequence. In some embodiments, the present invention provides a rodent having a germline genome comprising: (a) a first engineered endogenous immunoglobulin kappa light chain locus comprising: (i) one or more human Vλ gene segments, (ii) one or more human Jλ gene segments, and (iii) Cλ gene, wherein the one or more human Vλ gene segments and the one or more human Jλ gene segments are operatively linked to the Cλ gene, and wherein the rodent lacks a rodent Cκ gene at the first engineered endogenous immunoglobulin κ locus; and (b) a second engineered endogenous immunoglobulin kappa light chain locus, further comprising: (i) one or more human Vκ gene segments, and (ii) one or more human Jκ gene segments, One or more human Vκ gene segments and one or more human Jκ gene segments are operably linked to a CK gene. In some embodiments, the CK gene is an endogenous rodent CK gene. In some embodiments, the rodent genome further comprises a nucleic acid sequence encoding an exogenous terminal deoxynucleotidyl transferase (TdT) operably linked to a transcriptional control unit. In some embodiments, the transcriptional control unit comprises a RAG1 transcriptional control unit, a RAG2 transcriptional control unit, an immunoglobulin heavy chain transcriptional control unit, an immunoglobulin kappa light chain transcriptional control unit, an immunoglobulin lambda light chain transcriptional control unit, or any combination thereof. In some embodiments, the nucleic acid sequence encoding the exogenous TdT is located in an immunoglobulin kappa light chain locus, an immunoglobulin lambda light chain locus, an immunoglobulin heavy chain locus, a RAG1 locus, or a RAG2 locus. In some embodiments, the TdT is human TdT. In some embodiments, the TdT is a short isoform of TdT (TdTS). In some embodiments, the rodent genome further comprises a nucleic acid sequence encoding an exogenous terminal deoxynucleotidyl transferase (TdT) operably linked to a transcriptional control unit. In some embodiments, the transcriptional control unit comprises a RAG1 transcriptional control unit, a RAG2 transcriptional control unit, an immunoglobulin heavy chain transcriptional control unit, an immunoglobulin kappa light chain transcriptional control unit, an immunoglobulin lambda light chain transcriptional control unit, or any combination thereof. In some embodiments, the nucleic acid sequence encoding exogenous TdT is located on an immunoglobulin kappa light chain locus, an immunoglobulin lambda light chain locus, an immunoglobulin heavy chain locus, a RAG1 locus, or a RAG2 locus. In some embodiments, TdT is human TdT. In some embodiments, TdT is a short isoform of TdT (TdTS). In some embodiments, the rodents described herein comprise a nucleic acid sequence encoding an exogenous terminal deoxynucleotidyl transferase (TdT) operably linked to a transcriptional control element in their germline genome and exhibit at least a 1.2-fold, at least a 1.5-fold, at least a 1.75-fold, at least a 2-fold, at least a 3-fold, at least a 4-fold, at least a 5-fold increase in light chain junction diversity (e.g., representation of included light chain variable domains) compared to a comparable mouse (e.g., littermate) that does not comprise an exogenous terminal deoxynucleotidyl transferase (TdT) operably linked to a transcriptional control element in its germline genome. In some embodiments, junction diversity is measured by unique CDR3 / 10,000 reads. In some embodiments, junction diversity is measured by unique CDR3 / 10,000 reads. In some embodiments, the rodents described herein include a nucleic acid sequence encoding an exogenous terminal deoxynucleotidyl transferase (TdT) operably linked to a transcriptional control unit in their germline genome, and at least 25%, at least 30%, at least 35%, at least 40%, 45%, at least 50%, at least 55%, at least 60%, at least 65% of the light chains (e.g., lambda and / or kappa light chains) produced by the rodent have non-templated incorporation. In various embodiments, the non-human animals, non-human cells, or non-human tissues described herein are rodents, rodent cells, or rodent tissues; in some embodiments, mice, mouse cells, or mouse tissues; in some embodiments, rats, rat cells, or rat tissues. In some embodiments, the mice, mouse cells, or mouse tissues described herein comprise a genetic background comprising a 129 strain, a BALB / c strain, a C57BL / 6 strain, a mixed 129xC57BL / 6 strain, or a combination thereof. Brief description of selected sequences in the sequence listing The following are representative nucleic acid and amino acid sequences of various immunoglobulin constant regions from mouse, rat, or human lambda genes. Nucleic acid sequences of immunoglobulin genes and polypeptide sequences can be obtained from the International Immunogenetics Information System website at www.imgt.org. Mouse Cλ1 DNA (SEQ ID NO: 1): Mouse Cλ1 amino acid (SEQ ID NO: 2): Mouse Cλ2 DNA (SEQ ID NO: 3): Mouse Cλ2 amino acid (SEQ ID NO: 4): Mouse Cλ3 DNA (SEQ ID NO: 5): Mouse Cλ3 amino acid (SEQ ID NO: 6): Rat Cλ1 DNA (SEQ ID NO: 7): Rat Cλ1 amino acid (SEQ ID NO: 8): Rat Cλ2 DNA (SEQ ID NO: 9): Rat Cλ2 amino acid (SEQ ID NO: 10): Rat Cλ3 DNA (SEQ ID NO: 11): Rat Cλ3 amino acid (SEQ ID NO: 12): Rat Cλ4 DNA (SEQ ID NO: 13): Rat Cλ4 amino acid (SEQ ID NO: 14): Human Cλ1 DNA (SEQ ID NO: 15): Human Cλ1 amino acid (SEQ ID NO: 16): Human Cλ2 DNA (SEQ ID NO: 17): Human Cλ2 amino acid (SEQ ID NO: 18): Human Cλ3 DNA (SEQ ID NO: 19): Human Cλ3 amino acid (SEQ ID NO: 20): Human Cλ6 DNA (SEQ ID NO: 21): Human Cλ6 amino acid (SEQ ID NO: 22): Human Cλ7 DNA (SEQ ID NO: 23): Human Cλ7 amino acid (SEQ ID NO: 24): definition The scope of the present invention is defined by the appended claims and is not limited to certain embodiments described herein. Those skilled in the art who read this specification will appreciate that various modifications may be equivalent to the embodiments described herein or fall within the scope of the claims. In general, unless otherwise expressly stated, the terms used herein are consistent with their meanings as understood in the art. Explicit definitions of certain terms are provided below; the meaning of these and other terms in specific examples in this specification will be clear to those skilled in the art from the context. Additional definitions of the following and other terms are set forth throughout the specification. Patent and non-patent references cited in this specification, or relevant portions thereof, are incorporated herein by reference in their entirety. The use of ordinal terms such as "first," "second," "third," etc. in the scope of a patent application to modify the application element itself does not mean that this application element takes precedence over another, or has any priority, precedence or method sequence in time. It is only used as an indicator to distinguish a claimed element with a specific name from another element with the same name (but is used to distinguish these application elements using ordinal terms). The term " About" and " "Approximately" is an equivalent term. Any number used in this application, whether about or approximate, is meant to include any normal fluctuations understood by ordinary technicians in the relevant field. Unless expressly stated to the contrary, the articles "a" and "an" in the specification and claims should be understood to include plural referents. If one, more than one, or all of the group members of a group are present, used, or otherwise relevant in the product or method mentioned, then a statement or description including "or" between one or more members of the group is deemed satisfied, unless otherwise stated to the contrary or obvious from the context. The invention includes such embodiments in which exactly one member of the group is present, used, or otherwise relevant in the product or method mentioned. The invention also includes embodiments in which more than one or all of the group members are present, used, or otherwise relevant in the product or method mentioned. In addition, it should be understood that the invention covers all variations, combinations, and permutations in which one or more limitations, elements, clauses, descriptive terms, etc. from the listed claims are introduced into another claim based on the same basic claim (or, for that matter, any other claim), unless otherwise stated or unless it is clear to one of ordinary skill in the art that a contradiction or inconsistency would arise. Where elements are presented as a list (e.g., in a Markush group or similar format), it is understood that each subgroup is also disclosed and that any element can be removed from the group. It is understood that, in general, where the present invention or aspects of the present invention refer to including specific elements, features, etc., certain embodiments of the present invention or aspects of the present invention are composed of or essentially consist of these elements, functions, etc. For the purpose of simplicity, these embodiments are not specifically described in so many words herein. It is also understood that any embodiment or aspect of the present invention can be explicitly excluded from the claims regardless of whether a specific exclusion is described in the specification. Administration: As used herein, includes administering a composition to a subject or system (e.g., a cell, organ, tissue, organism, or a component thereof or a group of components thereof). One skilled in the art will appreciate that the route of administration may vary depending on, for example, the subject or system to which the composition is administered, the nature of the composition, the purpose of administration, and the like. For example, in certain embodiments, administration to an animal subject (e.g., to a human or rodent) may be intrabronchial (including via bronchial instillation), oral, enteral, intradermal, intraarterial, intradermal, intragastric, intramedullary, intramuscular, intranasal, intraperitoneal, intrathecal, intravenous, intraventricular, mucosal, nasal, oral, rectal, subcutaneous, sublingual, topical, tracheal (including via intratracheal instillation), transdermal, vaginal, and / or vitreous. In some embodiments, administration may include intermittent administration. In some embodiments, administration may include continuous administration (e.g., perfusion) for at least a selected period of time. Ameliorate: As used herein, includes prevention, alleviation or relief of a condition, or improvement of a condition of an individual. Alleviation includes but does not require complete recovery or complete prevention of a disease, disorder or condition. About: Applied to one or more values ​​of interest, including values ​​similar to the reference value. In certain embodiments, the term “ Approximately" or "About" refers to a range that falls within ±10% (greater or less than) of the reference value, unless otherwise stated, or a value that is obvious from the context (unless such number exceeds 100% of the possible value). Biologically active: As used herein, refers to any property of an agent that is active in a biological system, in vitro or in vivo (e.g., within an organism). For example, an agent that has a biological effect within an organism when present in that organism is considered to be biologically active. In certain embodiments, where a protein or polypeptide is biologically active, a portion of the protein or polypeptide that shares at least one biological activity of the protein or polypeptide is generally referred to as a " The "biologically active" portion. Comparable: As used herein, refers to two or more agents, entities, situations, sets of conditions, etc., which may not be identical to one another but are sufficiently similar to permit a comparison between them such that conclusions can reasonably be drawn based on the observed differences or similarities. In this context, one of ordinary skill in the art will understand that in any particular case, a certain degree of identity is required for two or more such agents, entities, situations, sets of conditions, etc. to be considered comparable. Conservative: As used herein, refers to examples describing conservative amino acid substitutions, including replacing an amino acid residue with another amino acid residue having a side chain R group with similar chemical properties (e.g., charge or hydrophobicity). In general, conservative amino acid substitutions do not substantially alter the functional properties of the protein of interest, such as the ability of a receptor to bind a ligand. Examples of amino acid groups with side chains of similar chemical properties include: aliphatic side chains such as glycine (Gly, G), alanine (Ala, A), valine (Val, V), leucine (Leu, L), and isoleucine (Ile, I); aliphatic hydroxyl side chains such as serine (Ser, S) and threonine (Thr, T); amide-containing side chains such as asparagine (Asn, N) and glutamine (Gln, Gln, N); and hydroxyl-containing side chains such as threonine (Thr, T). , Q); aromatic side chains, such as phenylalanine (Phe, F), tyrosine (Tyr, Y), and tryptophan (Trp, W); basic side chains, such as lysine (Lys, K), arginine (Arg, R), and histidine (His, H); acidic side chains, such as aspartic acid (Asp, D) and glutamate (Glu, E); and sulfur-containing side chains, such as cysteine ​​(Cys, C) and methionine (Met, M). Conservative amino acid substitutions include, for example, valine / leucine / isoleucine (Val / Leu / Ile, V / L / I), phenylalanine / tyrosine (Phe / Tyr, F / Y), lysine / arginine (Lys / Arg, K / R), alanine / valine (Ala / Val, A / V), glutamine / aspartate (Glu / Asp, E / D), and asparagine / glutamine (Asn / Gln, N / Q). In some embodiments, conservative amino acid substitutions can be substitutions of any native residue in the protein with alanine, for example, for alanine scanning mutagenesis. In some embodiments, conservative substitutions are made that have positive values ​​in the PAM250 log-likelihood matrix, as disclosed in Gonnet, GH et al., 1992, Science 256: 1443-1445, which is incorporated herein by reference in its entirety. In some embodiments, substitutions are moderately conservative substitutions that have non-negative values ​​in the PAM250 log-likelihood matrix. Control group: as used herein, refers to " The term "control" is used literally to define a standard to which results are compared. Typically, a control group is used to enhance the integrity of an experiment by isolating variables so that conclusions can be drawn about those variables. In some embodiments, a control group is run concurrently with a test reaction or assay to provide a comparison reaction or assay. The control group also included control group animals." A "control animal" may have modifications as described herein, modifications other than those described herein, or no modifications (i.e., a wild-type animal). In one experiment, a " test” (i.e., the variable being tested). In the second experiment, “ A "control group" is a group in which the variable being tested is not used. In some embodiments, the control group is a historical control (i.e., a previously performed test or experiment, or a previously known quantity or result). In some embodiments, the control group is or includes a printed or otherwise saved record. The control group can be a positive control group or a negative control group. Disruption: As used herein, refers to the result of a homologous recombination event with a DNA molecule (e.g., with an endogenous homologous sequence, such as a gene or locus). In some embodiments, a disruption can result in or represent an insertion, deletion, substitution, replacement, missense mutation, or frameshift of a DNA sequence, or any combination thereof. Insertion can include insertion of an entire gene or a gene fragment, such as an exon, which can be a source of non-endogenous sequence (e.g., a heterologous sequence). In some embodiments, a disruption can increase the expression and / or activity of a gene or gene product (e.g., a polypeptide encoded by a gene). In some embodiments, a disruption can decrease the expression and / or activity of a gene or gene product. In some embodiments, a disruption can alter the sequence of a gene or encoded gene product (e.g., an encoded polypeptide). In some embodiments, a disruption can truncate or fragment a gene or encoded gene product (e.g., an encoded polypeptide). In some embodiments, a disruption can extend a gene or encoded gene product. In some such embodiments, a disruption can result in the assembly of a fusion polypeptide. In some embodiments, a disruption can affect the level of a gene or gene product, but not its activity. In some embodiments, the destruction may affect the activity of a gene or gene product, but not the content. In some embodiments, the destruction may not significantly affect the content of a gene or gene product. In some embodiments, the destruction may not significantly affect the activity of a gene or gene product. In some embodiments, the destruction may not significantly affect the content or activity of a gene or gene product. Determine, measure, evaluate, assess, test and Assay: are used interchangeably herein to refer to any form of measurement, including determining the presence or absence of an element. These terms include quantitative and / or qualitative measurements. Assays may be relative or absolute. Testing for its presence can determine how much of something is present and / or whether it exists at all. Endogenous Promoter: as used herein refers to a promoter naturally associated with an endogenous gene, eg, in a wild-type organism. Modified: As used herein, generally refers to an aspect that has been artificially manipulated. For example, in some embodiments, a polynucleotide is considered "modified" when two or more sequences are not linked together in their natural order but are artificially manipulated to be directly linked to a modified polynucleotide. "modified". In some embodiments, the modified polynucleotide may comprise a regulatory sequence found in nature, which is operably linked to a first coding sequence but not to a second coding sequence, and which may be artificially linked so as to be operably linked to a second coding sequence. Furthermore, or additionally, in some embodiments, a first and a second nucleic acid sequence, each encoding a polypeptide unit or domain that is not linked to each other in nature, may be linked to each other in a single modified polynucleotide. In contrast, in some embodiments, if a cell or organism has been manipulated so that its genetic information has been changed (for example, new genetic material that did not previously exist has been introduced, or previously existing genetic material has been changed or removed), it may be considered to be "modified". As will be understood by those of ordinary skill in the art, the descendants of a modified polynucleotide or cell are still generally referred to as " Even if the actual operation is performed on the previous entity. In addition, as will be understood by those skilled in the art, various methods can be used, which can achieve the "modified" as described herein. Transformation". For example, in some embodiments, " "Transformation" may involve screening or designing (e.g., nucleic acid sequences, polypeptide sequences, cells, tissues, and / or organisms) by performing analysis or comparison using a computer system program, or otherwise analyzing, suggesting, and / or screening sequences, changes, etc.). In addition, or in addition, in some embodiments, " change "Creation" can involve the use of In vitro chemical synthesis methods, and / or recombinant nucleic acid techniques, such as nucleic acid multiplication (e.g., via polymerase chain reaction), hybridization, mutation, transformation, transfection, and / or any of various controlled pairing methods. As will be appreciated by those skilled in the art, a variety of established such techniques (e.g., for recombinant DNA, oligonucleotide synthesis, tissue culture, and transformation (e.g., electroporation, lipofection, etc.)) are well known in the art and are described in various general and more specific references cited and / or discussed in this specification. See, for example, Sambrook et al., Molecular Cloning: A Laboratory Manual, 2nd ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, 1989, and Principles of Gene Manipulation: An Introduction to Genetic Manipulation, 5th ed., Old, RW and SB Primrose, eds., Blackwell Science, Inc., 1994, incorporated herein by reference in their entireties. Functional: As used herein, refers to a form or fragment of an entity (e.g., a gene or gene segment) that has a specific property (e.g., forms part of a coding sequence) and / or activity. For example, in the case of immunoglobulins, the variable regions are encoded by unique gene segments (i.e., V, D, and / or J) that are assembled (or recombined) to form a functional coding sequence. When present in a genome, the gene segments are organized as aggregates, although variations do occur. A "functional" gene segment is a gene segment that is represented in an expressed sequence (i.e., a variable region) where the corresponding genomic DNA has been isolated (i.e., replicated) and identified by sequencing. Some immunoglobulin gene segment sequences contain open reading frames and are considered functional despite not being present in the expressed library, while other immunoglobulin gene segment sequences contain mutations (e.g., point mutations, insertions, deletions, etc.) that result in stop codons and / or truncated sequences that subsequently render such gene segment sequences incapable of exerting the properties and / or activities associated with the non-mutated sequence. These sequences are not present as expressed sequences and are therefore classified as pseudogenes. Gene: as used herein, refers to a DNA sequence in a chromosome that encodes a product (e.g., an RNA product and / or a polypeptide product). In some embodiments, a gene includes a coding sequence (i.e., a sequence that encodes a specific product). In some embodiments, a gene includes a non-coding sequence. In some specific embodiments, a gene may include coding (e.g., exons) and non-coding (e.g., introns) sequences. In some embodiments, a gene may include one or more regulatory sequences (e.g., promoters, enhancers, etc.), and / or intron sequences, which, for example, can control or influence one or more aspects of gene expression (e.g., cell type-specific expression, inducible expression, etc.). For the sake of clarity, we note that, as used in the present invention, the term " "Gene" generally refers to a portion of a nucleic acid encoding a polypeptide or a fragment thereof; the term may optionally include regulatory sequences, as will be clear to one of ordinary skill in the art from the context. This definition does not exclude the term " The term "gene" is not intended to refer to non-protein-coding expression units, but rather to clarify that in most cases the term is used herein to refer to a nucleic acid encoding a polypeptide. Heterologous: As used herein, refers to an agent or entity that is derived from a different source. For example, when used to refer to a polypeptide, gene, or gene product present in a particular cell or organism, the term clarifies that the polypeptide, gene, or gene product is: 1) artificially produced; 2) artificially introduced into the cell or organism (or a precursor thereof) (e.g., by genetic engineering); and / or 3) not naturally produced or present in the relevant cell or organism (e.g., the relevant cell type or organism type). "Heterologous" also includes polypeptides, genes, or gene products that are normally present in a particular native cell or organism, but that have been altered or modified, for example, by mutation or placement under the control of a non-naturally associated, and in some embodiments, non-endogenous, regulatory element (e.g., promoter). Host cell: as used herein, refers to a cell into which a nucleic acid or protein has been introduced. Those skilled in the art, upon reading this disclosure, will understand that these terms refer not only to a particular individual cell, but also to the progeny of such a cell. Because certain modifications may occur in the progeny due to mutations or environmental influences, these progeny may not actually be the same as the parent cell, but are still included in the term " In some embodiments, the host cell is or comprises a prokaryotic or eukaryotic cell. Generally, a host cell is any cell suitable for receiving and / or producing heterologous nucleic acid or protein, regardless of the kingdom of life to which the cell belongs. Exemplary cells include prokaryotes and eukaryotes (unicellular or multicellular), bacterial cells (e.g., Escherichia coli ( Escherichia coli), Bacillus spp. Bacillus spp.), Streptomyces spp. Streptomyces spp.), mycobacterial cells, fungal cells, yeast cells (e.g., Saccharomyces cerevisiae ( Saccharomyces cerevisiae), pombe yeast ( Schizosaccharomyces pombe), methanol-loving yeast ( Pichia pastoris), methanol yeast ( Pichia methanolica), plant cells, insect cells (e.g., SF-9, SF-21, baculovirus-infected insect cells, Trichoplusia ni, etc.), non-human animal cells, human cells, or cell fusions, e.g., hybridomas or tetraploids. In some embodiments, the cells are human, monkey, ape, hamster, rat, or mouse cells. In some embodiments, the cell is a eukaryotic cell selected from the group consisting of CHO (e.g., CHO K1, DXB-11 CHO, Veggie-CHO), COS (e.g., COS-7), retinal cells, Vero, CV1, kidney cells (e.g., HEK293, 293 EBNA, MSR 293, MDCK, HaK, BHK), HeLa, HepG2, WI38, MRC 5, Colo205, HB 8065, HL-60 (e.g., BHK21), Jurkat, Daudi, A431 (epidermal), CV-1, U937, 3T3, L cells, C127 cells, SP2 / 0, NS-0, MMT 060562, Sertoli cells, BRL 3A cells, HT1080 cells, myeloma cells, tumor cells, and cell lines derived from the above. In some embodiments, the cell comprises one or more viral genes, such as retinal cells expressing viral genes (e.g., PER.C6® cells). In some embodiments, the host cell is or comprises an isolated cell. In some embodiments, the host cell is a part of a tissue. In some embodiments, the host cell is a part of an organism. Identical: As used in conjunction with sequence comparison herein, this refers to identity as determined by any of several different algorithms known in the art for determining nucleotide and / or amino acid sequence identity. In some embodiments, alignments are determined using ClustalW v.1.83 (slow), with an open gap penalty of 10.0, an extended gap penalty of 0.1, and a Gonnet similarity matrix (MACVECTOR TM 10.0.2, MacVector Inc., 2008). Substitution: As used herein, refers to a positional substitution in which a first nucleic acid sequence is located at the position of a second nucleic acid sequence in a chromosome (e.g., where the second nucleic acid sequence was previously (e.g., originally) located in the chromosome, e.g., located at the endogenous locus of the second nucleic acid sequence). The term "replacement" does not necessarily mean that the second nucleic acid sequence is removed from, for example, a locus or chromosome. In some embodiments, the second nucleic acid sequence and the first nucleic acid sequence are comparable to each other, e.g., the first and second sequences are homologous to each other, contain corresponding units (e.g., protein coding units, regulatory units, etc.), and / or have similar or identical sequences. In some embodiments, the first and / or second nucleic acid sequences include one or more promoters, enhancers, splice donor sites, splice acceptor sites, introns, exons, untranslated regions (UTRs); in some embodiments, the first and / or second nucleic acid sequences include one or more coding sequences. In some embodiments, the first nucleic acid sequence is a homolog or variant (e.g., a mutant) of the second nucleic acid sequence. In some embodiments, the first nucleic acid sequence is an ortholog or homolog of the second sequence. In some embodiments, the first nucleic acid sequence is or comprises a human nucleic acid sequence. In some embodiments, the first nucleic acid sequence is or comprises a human nucleic acid sequence and the second nucleic acid sequence is or comprises a rodent sequence (e.g., a mouse or rat sequence). In some embodiments, the first nucleic acid sequence is or comprises a human nucleic acid sequence and the second nucleic acid sequence is or comprises a human sequence. In some embodiments, the first nucleic acid sequence is a variant or mutant of the second sequence (i.e., a sequence that contains one or more sequence differences (e.g., substitutions) compared to the second sequence). The nucleic acid sequence thus configured may include one or more regulatory sequences that are part of the source nucleic acid sequence used to obtain the sequence thus configured (e.g., a promoter, enhancer, 5'- or 3'-untranslated region, etc.). For example, in various embodiments, the first nucleic acid sequence replaces an endogenous sequence with a heterologous sequence, such that the nucleic acid sequence (including the heterologous sequence) produces a gene product but does not express the endogenous sequence; the first nucleic acid sequence comprises an endogenous genomic sequence having a nucleic acid sequence encoding a polypeptide having a similar function to the polypeptide encoded by the endogenous sequence (e.g., the endogenous genomic sequence encodes a non-human variable region polypeptide (in whole or in part), and the DNA fragment encodes one or more human variable region polypeptides (in whole or in part)). In various embodiments, the human immunoglobulin gene segment or fragment thereof is located in the place of an endogenous non-human immunoglobulin gene segment or fragment. In vitro: as used herein refers to events that occur in an artificial environment, such as in a test tube or reaction vessel, in cell culture, etc., rather than within a multicellular organism. In vivo: As used herein, refers to events that occur within a multicellular organism, such as a human and / or non-human animal. In the context of cell-based systems, the term can be used to refer to events that occur within living cells (e.g., in vitro systems). Isolated: as used herein, refers to a substance and / or entity that is (1) separated from at least some of the components with which it was initially associated when it was created (whether in nature or in a laboratory setting), and / or (2) designed, produced, prepared, and / or manufactured by the hand of man. An isolated substance and / or entity may be separated from about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or greater than about 99% of the other components with which it was initially associated. In some embodiments, the isolated agent is separated from 10%-100%, 15%-100%, 20%-100%, 25%-100%, 30%-100%, 35%-100%, 40%-100%, 45%-100%, 50%-100%, 55%-100%, 60%-100%, 65%-100%, 70%-100%, 75%-100%, 80%-100%, 85%-100%, 90%-100%, 95%-100%, 96%-100%, 97%-100%, 98%-100%, or 99%-100% of the other components with which it was originally associated. In some embodiments, the isolated agent is separated from 10%-100%, 10%-99%, 10%-98%, 10%-97%, 10%-96%, 10%-95%, 10%-90%, 10%-85%, 10%-80%, 10%-75%, 10%-70%, 10%-65%, 10%-60%, 10%-55%, 10%-50%, 10%-45%, 10%-40%, 10%-35%, 10%-30%, 10%-25%, 10%-20%, or 10%-15% of the other components with which it was originally associated. In some embodiments, the isolated agent is separated from 11% to 99%, 12%-98%, 13%-97%, 14%-96%, 15%-95%, 20%-90%, 25%-85%, 30%-80%, 35%-75%, 40%-70%, 45%-65%, 50%-60%, or 55%-60% of the other components with which it was originally associated. In some embodiments, the isolated agent is about 80%, about 85%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or greater than about 99% pure. In some embodiments, the isolated agent is 80%-99%, 85%-99%, 90%-99%, 95%-99%, 96%-99%, 97%-99%, or 98%-99% pure.In some embodiments, the isolated agent is 80%-99%, 80%-98%, 80%-97%, 80%-96%, 80%-95%, 80%-90%, or 80%-85% pure. In some embodiments, the isolated agent is 85%-98%, 90%-97%, or 95%-96% pure. In some embodiments, a substance is "pure" if it is substantially free of other components. In some embodiments, as will be understood by those skilled in the art, a substance may be considered "pure" after being combined with certain other ingredients, for example, one or more carriers or excipients (e.g., buffers, solvents, water, etc.). separated" or even " "pure"; in such embodiments, the percentage or purity of the substance is calculated without these carriers or excipients. For exemplary purposes only, in some embodiments, a biopolymer such as a naturally occurring polypeptide or polynucleotide is considered "pure" when: "Isolated" means a polypeptide that a) is derived from a source other than that in which it is naturally associated, in whole or in part, with its accompanying components; b) is substantially free of other polypeptides or nucleic acids of the same species in which it is produced in nature; or c) is expressed by, or associated with components of, a cell or other expression system other than the species in which it is naturally produced. Thus, for example, in certain embodiments, a polypeptide that is chemically synthesized or synthesized in a system different from the natural cell system in which it is produced is considered "isolated". Alternatively, or additionally, in some embodiments, a polypeptide that has been subjected to one or more purification techniques may be considered an "isolated" polypeptide. An “isolated” polypeptide is one that is separated to some extent from other components with which it is: a) naturally associated; and / or b) originally associated during manufacture. locus or Locus: As used herein, refers to the location or position of a gene (or significant sequence), DNA sequence, or polypeptide-coding sequence on a chromosome in the genome of an organism. For example, " An “immunoglobulin locus” can refer to an immunoglobulin gene segment (e.g., V, D, J, or C), an immunoglobulin gene segment DNA sequence, an immunoglobulin gene segment-coding sequence, or the location of an immunoglobulin gene segment on a chromosome in the genome of an organism where the location of this sequence has been identified. An immunoglobulin locus" may comprise regulatory elements of an immunoglobulin gene segment, including but not limited to enhancers, promoters, 5' and / or 3' regulatory sequences or regions, or combinations thereof." An "immunoglobulin locus" may include intergenic DNA, e.g., DNA between gene segments that are normally located or present in a wild-type locus. One of ordinary skill in the art will appreciate that, in some embodiments, a chromosome may contain hundreds or even thousands of genes that, when compared between different species, may exhibit physical co-localization of similar genetic loci. Such genetic loci may be described as having shared synteny. Naturally occurring: As used herein, with respect to a biological element (e.g., a nucleic acid sequence), it means that a biological element can be found in a specific context and / or location, and has not been modified (e.g., genetically engineered) in a cell or organism (e.g., an animal). In other words, a sequence that naturally occurs in a specified context and / or location is not in a specified context and / or location as a result of modification (e.g., genetic engineering). For example, in an endogenous human immunoglobulin κ light chain locus, a sequence that naturally occurs adjacent to a human Jκ1 gene segment is a human Jκ1 gene segment that can be found adjacent to an endogenous human immunoglobulin κ light chain locus (without genetic engineering). In some embodiments, the sequence can be obtained, derived, and / or isolated from a cell or organism in which it naturally occurs. In some embodiments, the cell or organism is not the direct source of the sequence that naturally occurs in the cell or organism. For example, a corresponding sequence in a cell or organism can be identified and then produced or replicated via mechanisms known in the art. Non-human animal: As used herein, refers to any non-human vertebrate. In some embodiments, the non-human animal is a cyclostomide, bony fish, cartilaginous fish (e.g., sharks or rays), amphibians, reptiles, mammals, and birds. In some embodiments, the non-human animal is a mammal. In some embodiments, the non-human mammal is a primate, goat, sheep, pig, dog, cow, or rodent. In some embodiments, the non-human animal is a rodent, such as a rat or mouse. Nucleic acid: as used herein, refers to any compound and / or substance that is or can be added to an oligonucleotide chain. In some embodiments, “ "Nucleic acid" is a compound and / or substance that may be incorporated into an oligonucleotide chain via a phosphodiester bond. As is clear from the context, in some embodiments, " "Nucleic acid" refers to individual nucleic acid residues (eg, nucleotides and / or nucleosides); in some embodiments, " "Nucleic acid" refers to an oligonucleotide chain comprising individual nucleic acid residues. In some embodiments, "nucleic acid" is or comprises RNA; in some embodiments, " "Nucleic acid" is or comprises DNA. In some embodiments, " "Nucleic acid" is, comprises, or consists of one or more natural nucleic acid residues. In some embodiments, " "Nucleic acid" is, comprises or consists of one or more nucleic acid analogs. In some embodiments, nucleic acid analogs and " "nucleic acids" differ in that they do not utilize a phosphodiester backbone. For example, in some embodiments, " Nucleic acid is, contains or consists of one or more "peptide nucleic acids," which are known in the art and have peptide bonds rather than phosphodiester bonds in the backbone. Additionally or additionally, in some embodiments, " "nucleic acids" have one or more phosphorothioate and / or 5'-N-phosphoamidite bonds rather than phosphodiester bonds. In some embodiments, " A "nucleic acid" is, comprises, or consists of one or more natural nucleosides (e.g., adenosine, thymidine, guanosine, cytidine, uridine, deoxyadenosine, deoxythymidine, deoxyguanosine, and deoxycytidine). In some embodiments, " A "nucleic acid" is, comprises, or consists of one or more nucleoside analogs (e.g., 2-aminoadenosine, 2-thiothymidine, inosine, pyrrolopyrimidine, 3-methyladenosine, 5-methylcytidine, C-5 propynyl-cytidine, C-5 propynyl-uridine, 2-aminoadenosine, C5-bromouridine, C5-fluorouridine, C5-iodouridine, C5-propynyl-uridine, C5-propynyl-cytidine, C5-methylcytidine, 2-aminoadenosine, 7-deazaadenosine, 7-deazaguanosine, 8-oxoadenosine, 8-oxoguanosine, O(6)-methylguanine, 2-thiocytidine, methylated bases, intercalating bases, and combinations thereof). In some embodiments, compared to those in natural nucleic acids, " "Nucleic acids" comprise one or more modified sugars (eg, 2'-fluororibose, ribose, 2'-deoxyribose, arabinose, and hexose). In some embodiments, " A "nucleic acid" has a nucleotide sequence that encodes a functional gene product, such as an RNA or a polypeptide. In some embodiments, a " In some embodiments, the "nucleic acid" includes one or more introns. In some embodiments, "nucleic acid" includes one or more exons. "Nucleic acids" are prepared by isolation of one or more isolates from natural sources, enzymatic synthesis based on polymerization of a complementary template (in vivo or in vitro), replication in recombinant cells or systems, and chemical synthesis. In some embodiments, " A “nucleic acid” is at least, but not limited to, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 20, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, 500, 600, 700, 800, 900, 1000, 1500, 2000, 2500, 3000, 3500, 4000, 4500, 5000 or more residues in length. In some embodiments, a “nucleic acid” is at least, but not limited to, 3, 4, 5, 6, 7, 8, 9, 10 Nucleic acid" is single stranded; in some embodiments, a " Nucleic acid" is double-stranded. In some embodiments, " A "nucleic acid" has a nucleotide sequence comprising at least one unit encoding a peptide or a complementary sequence encoding a peptide. In some embodiments, " Nucleic acids have enzyme activity. Operably linked: as used herein, refers to a juxtaposition wherein the elements described are in a relationship permitting them to function in their intended manner. Control sequence" "Operably linked to a coding sequence" is linked in such a way that expression of the coding sequence is achieved under conditions compatible with the control sequences. "Operably linked" sequences include both expression control sequences that are contiguous with the gene of interest, as well as expression control sequences that act in trans or remotely to control the gene of interest (or sequence of interest). The term " "Expression control sequences" include polynucleotide sequences that are necessary to affect the expression and processing of coding sequences to which they are ligated." "Expression control sequences" include: appropriate transcription initiation, termination, promoter and enhancer sequences; efficient RNA processing signals, such as splicing and polyadenylation signals; sequences that stabilize cytoplasmic mRNA; sequences that enhance translation efficiency (i.e., Kozak consensus sequences); sequences that enhance polypeptide stability; and, when desired, sequences that enhance polypeptide secretion. The nature of such control sequences varies depending on the host organism. For example, in prokaryotes, such control sequences typically include a promoter, a ribosome binding site, and a transcription termination sequence, while in eukaryotes, such control sequences typically include a promoter and a transcription termination sequence. The term " "Control sequences" are meant to include components whose presence is essential for expression and processing, and can also include additional components whose presence is advantageous, such as leader sequences and fusion partner sequences. Physiological conditions: as used herein, refers to conditions technically understood for the survival and / or replication of a cell or organism. In some embodiments, the term includes external or internal conditions that may occur naturally in an organism or cell system. In some embodiments, physiological conditions are conditions that exist in the human or non-human animal body, particularly conditions that exist at and / or within a surgical site. Physiological conditions typically include, for example, a temperature range of 20-40°C, 1 atmosphere of pressure, a pH of 6-8, a glucose concentration of 1-20 mM, an atmospheric oxygen concentration, and gravity on Earth. In some embodiments, conditions in the laboratory are manipulated and / or maintained at physiological conditions. In some embodiments, physiological conditions are located within an organism. Polypeptide: As used herein, refers to any polymeric chain of amino acids. In some embodiments, a polypeptide has a naturally occurring amino acid sequence. In some embodiments, a polypeptide has an amino acid sequence that does not occur in nature. In some embodiments, a polypeptide has an amino acid sequence that contains parts that occur separately from each other in nature (i.e., from two or more different organisms, such as human and non-human parts). In some embodiments, a polypeptide has an amino acid sequence that is designed and / or generated artificially. In some embodiments, a polypeptide has an amino acid sequence that is encoded by a sequence that does not occur in nature (e.g., a modified sequence that was designed and / or generated artificially to encode the polypeptide). Recombinant: As used herein, refers to a polypeptide that is designed, engineered, prepared, expressed, created, or isolated by recombinant means, such as a polypeptide expressed using a recombinant expression vector transfected into a host cell, a polypeptide isolated from a recombinant, combinatorial human polypeptide library (Hoogenboom, H.R., 1997, TIB Tech. 15:62-70; Azzazy, H. and WE Highsmith, 2002, Clin. Biochem. 35:425-45; Gavilondo, J.V. and J.W. Larrick, 2002, BioTechniques 29:128-45; Hoogenboom H., and P. Chames, 2000, Immunol. Today 21:371-8, the contents of which are incorporated herein by reference in their entireties), a polypeptide isolated from an animal (e.g., a mouse) that has been genetically engineered to include human immunoglobulin gene antibodies (see, e.g., Taylor, L.D. et al., 1992, Nucl. Acids Res. 20: 6287-95; Kellermann, SA. and LL Green, 2002, Curr. Opin. Biotechnol. 13: 593-7; Little, M. et al., 2000, Immunol. Today 21:364-70; Osborn, MJ et al., 2013, J. Immunol. 190:1481-90; Lee, EC. et al., 2014, Nat. Biotech. 32(4):356-63; Macdonald, LE et al., 2014, Proc. Natl. Acad. Sci. USA 111(14):5147-52; Murphy, AJ et al., 2014, Proc. Natl. Acad. Sci. USA 111(14):5153-8, the contents of which are incorporated herein by reference in their entirety), or by preparing, expressing, producing or isolating the polypeptide in any other manner that involves splicing selected sequence units to each other. In some embodiments, one or more such selected sequence units are found in nature. In some embodiments, one or more such selected sequence units are located in Designed in silico. In some embodiments, one or more such selected sequence units are derived from mutations of known sequence units (e.g., in vivo or in vitro), such as from natural or synthetic (e.g., artificial) sources. For example, in some embodiments, the recombinant polypeptide is composed of a sequence found in the genome of a source organism of interest (e.g., human, mouse, etc.). In some embodiments, the recombinant polypeptide has an amino acid sequence that is derived from a mutation (e.g., in vitro or in vivo, e.g., in a non-human animal), such that the amino acid sequence of the recombinant polypeptide (when derived from and related to the polypeptide sequence) may not naturally occur in the genome of the non-human animal in vivo. Reference: As used herein, refers to a standard or control reagent, animal, group, individual, population, sample, sequence, or value, which is compared to the reagent, animal, group, individual, population, sample, sequence, or value of interest. In some embodiments, the reference reagent, animal, group, individual, population, sample, sequence, or value is tested and / or determined substantially simultaneously with the reagent, animal, group, individual, population, sample, sequence, or value of interest to be tested or determined. In some embodiments, the reference reagent, animal, group, individual, population, sample, sequence, or value is an empirical reference, optionally embodied in a tangible medium. In some embodiments, the reference refers to a control group. References” also include Reference Animals." A "reference animal" can have modifications as described herein, modifications other than those described herein, or no modifications (i.e., a wild-type animal). Generally, as understood by those skilled in the art, a reference agent, animal, group, individual, population, sample, sequence, or value is assayed or identified under comparable conditions in which the agent, animal (e.g., mammal), group, individual, population, sample, sequence, or value of interest is assayed or identified. Substitution: As used herein, refers to a "replacement" found in a host locus (e.g., in a genome) A "replaced" nucleic acid sequence (e.g., gene) is removed from the locus and a different " In some embodiments, the substituted nucleic acid sequence and the replacing nucleic acid sequence are equivalent to each other, that is, for example, they are homologous to each other, contain corresponding units (e.g., protein-coding units, regulatory units, etc.), and / or have similar or identical sequences. In some embodiments, the substituted nucleic acid sequence includes one or more of a promoter, an enhancer, a splice donor site, a splice acceptor site, an intron, an exon, and an untranslated region (UTR); in some embodiments, the replacing nucleic acid sequence includes one or more coding sequences. In some embodiments, the replacing nucleic acid sequence is a homolog or variant (e.g., a mutant) of the substituted nucleic acid sequence. In some embodiments, the replacing nucleic acid sequence is an ortholog or homolog of the substituted sequence. In some embodiments, the replacing nucleic acid sequence is or comprises a human nucleic acid sequence. In some embodiments, including wherein the replacing nucleic acid sequence is or comprises a human nucleic acid sequence, and the substituted nucleic acid sequence is or comprises a rodent sequence (e.g., a mouse or rat sequence). In some embodiments, including wherein the replacing nucleic acid sequence is or comprises a human nucleic acid sequence, and the substituted nucleic acid sequence is or comprises a rodent sequence (e.g., a mouse or rat sequence). The nucleic acid sequence is or comprises a human sequence. In some embodiments, the replacing nucleic acid sequence is a variant or mutant of the replaced sequence (i.e., a sequence having one or more sequence differences, such as substitutions, compared to the replaced sequence). The nucleic acid sequence thus configured may include one or more regulatory sequences that are part of the source nucleic acid sequence used to obtain the sequence thus configured (e.g., a promoter, enhancer, 5'- or 3'-untranslated region, etc.). For example, in various embodiments, the substitution is a replacement of an endogenous sequence with a heterologous sequence, which results in the nucleic acid sequence thus configured being replaced. (including heterologous sequences) can produce gene products but not express the endogenous sequence; the replacement is an endogenous genomic sequence having a nucleic acid sequence that encodes a polypeptide with similar function to the polypeptide encoded by the endogenous sequence (e.g., the endogenous genomic sequence encodes a non-human variable region polypeptide (in whole or in part), and the DNA fragment encodes one or more human variable region polypeptides (in whole or in part)). In various embodiments, an endogenous non-human immunoglobulin gene segment or fragment thereof is replaced with a human immunoglobulin gene segment or fragment thereof. Substantially: as used herein, refers to the qualitative condition of exhibiting all or nearly all or some degree of the characteristics or properties of interest. One of ordinary skill in the art of biology will understand that biological and chemical phenomena rarely, if ever, are complete and / or proceed completely or achieve or avoid an absolute result. Therefore, the term " “Substantially” is used to cover the potential lack of integrity inherent in many biological and chemical phenomena. Substantial similarity: as used herein, refers to a comparison between amino acid or nucleic acid sequences. As understood by those skilled in the art, two sequences are generally considered to be "similar" if they have similar residues (e.g., amino acids or nucleotides) at corresponding positions. As is understood in the art, although similar residues may be identical residues (see also below), Although substantial identity is not essential, similar residues may also have non-equivalent residues with appropriately comparable structural and / or functional characteristics. For example, as is well known to those skilled in the art, certain amino acids are generally classified as " Hydrophobicity" or " Hydrophilic" amino acids, and / or have " Polarity" or " nonpolar" side chain. Replacing one amino acid with another of the same type is generally considered a " Typical amino acid classifications are summarized in the table below. As is well known in the art, amino acid or nucleic acid sequences can be compared using any of a variety of algorithms, including those available in commercially available computer programs, such as BLASTN for nucleotide sequences, and BLASTP, Gapped BLAST, and PSI-BLAST for amino acid sequences. Examples of such programs are described in Altschul, SF et al., 1990, J. Mol. Biol., 215(3):403-10; Altschul, SF et al., 1996, Meth. Enzymol. 266:460-80; Altschul, SF et al., 1997, Nucleic Acids Res., 25:3389-402; Baxevanis, AD and BF F. Ouellette (eds.) Bioinformatics: A Practical Guide to the Analysis of Genes and Proteins, Wiley, 1998; and Misener et al. (eds.) Bioinformatics Methods and Protocols, Methods in Molecular Biology, Vol. 132, Humana Press, 1998, incorporated herein by reference in their entireties. In addition to identifying similar sequences, the above programs typically provide an indication of similarity. In some embodiments, two sequences are considered substantially similar if at least, for example, but not limited to, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more of the corresponding residues are similar (e.g., identical or include conservative substitutions) along a relevant stretch of residues. In some embodiments, the relevant stretch is an entire sequence (e.g., a gene sequence, a gene fragment, a sequence encoding a domain, a polypeptide, or a domain). In some embodiments, the relevant stretch is at least 9, 10, 11, 12, 13, 14, 15, 16, 17 or more residues. In some embodiments, the relevant stretch is at least 10, 15, 20, 25, 30, 35, 40, 45, 50 or more residues. In some embodiments, the relevant stretch includes contiguous residues along the entire sequence. In some embodiments, the relevant stretch includes discontinuous residues along the entire sequence, for example, discontinuous residues that are brought together by the folded conformation of the polypeptide or a portion thereof. Substantial identity: as used herein, refers to a comparison between amino acid or nucleic acid sequences. As understood by those skilled in the art, two sequences are generally considered to be "substantial identity" if they contain the same residues (e.g., amino acids or nucleotides) at corresponding positions. As is well known in the art, amino acid or nucleic acid sequences can be compared using any of a variety of algorithms, including those available in commercially available computer programs, such as BLASTN for nucleotide sequences, and BLASTP, Gapped BLAST, and PSI-BLAST for amino acid sequences. Examples of such programs are described in Altschul, SF et al., 1990, J. Mol. Biol., 215(3): 403-10; Altschul, SF et al., 1996, Meth. Enzymol. 266: 460-80; Altschul, SF et al., 1997, Nucleic Acids Res., 25: 3389-402; Baxevanis, AD and BF F. Ouellette (eds.) Bioinformatics: A Practical Guide to the Analysis of Genes and Proteins, Wiley, 1998; and Misener et al. (eds.) Bioinformatics Methods and Protocols, Methods in Molecular Biology, Vol. 132, Humana Press, 1998, is incorporated herein by reference in its entirety. In addition to identifying identical sequences, the above-mentioned programs generally provide an indication of the degree of identity. In some embodiments, two sequences are considered to be substantially identical if at least, for example, but not limited to, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more of the corresponding residues are identical over the relevant stretch of residues. In some embodiments, the relevant stretch of residues is a complete sequence. In some embodiments, the relevant stretch is, for example, but not limited to, at least 10, 15, 20, 25, 30, 35, 40, 45, 50 or more residues. Targeting constructs or Targeting vector: As used herein, refers to a polynucleotide molecule comprising a targeting region. The targeting region comprises a sequence that is identical or substantially identical to a sequence in a target cell, tissue, or animal, and integrates the targeting construct into a location within the genome of the cell, tissue, or animal via homologous recombination. Also included and described herein are methods for targeting a target cell, tissue, or animal using a site-specific recombinase recognition site (e.g., loxP or Frt site) targeting region. In some embodiments, the targeting constructs described herein further comprise a nucleic acid sequence or gene of particular interest, a selection marker, a control and / or regulatory sequence, and other nucleic acid sequences that allow for recombination mediation via exogenously added proteins that assist or promote recombination involving such sequences. In some embodiments, the targeting constructs described herein further comprise all or part of a gene of interest, wherein the gene of interest is a heterologous gene encoding a polypeptide that has, in whole or in part, a function similar to that of a protein encoded by an endogenous sequence. In some embodiments, the targeting constructs described herein further comprise all or part of a humanized gene of interest, wherein the humanized gene of interest encodes, in whole or in part, a polypeptide that has a function similar to that of an endogenous sequence. In some embodiments, the targeting constructs (or targeting vectors) may comprise a nucleic acid sequence that is artificially manipulated. For example, in some embodiments, a targeting construct (or targeting vector) can be constructed to include an engineered or recombinant polynucleotide comprising two or more sequences that are not linked together in this order in nature, but are artificially manipulated so that the engineered or recombinant polynucleotides are directly linked to each other. Genetically modified or Transgenic construct: As used herein, refers to a nucleic acid sequence (encoding, for example, a polypeptide of interest (in whole or in part)) that has been introduced into a cell through human manipulation, such as by the methods described herein. A transgene can be partially or completely heterologous, i.e., foreign, to the genetically modified animal or cell into which it is introduced. A transgene can include one or more transcriptional regulatory sequences and any other nucleic acids, such as introns or promoters, that may be necessary for expression of the selected nucleic acid sequence. Genetically modified non-human animal or genetically engineered non-human animal: used interchangeably herein, refers to any non-naturally occurring non-human animal, wherein one or more cells of the non-human animal contain heterologous nucleic acid and / or a gene encoding a polypeptide of interest (in whole or in part). For example, in some embodiments, " genetically modified non-human animals" or A "genetically modified non-human animal" refers to a non-human animal that contains a transgene or transgenic construct, as described herein. In some embodiments, heterologous nucleic acids and / or genes are introduced into a cell directly or indirectly by intentional genetic manipulation, such as by microinjection or infection with a recombinant virus, into a precursor cell. The term genetic manipulation does not include typical breeding techniques, but rather involves the introduction of recombinant DNA molecules. Such molecules can be integrated into a chromosome or can be extrachromosomal replicating DNA. The term " genetically modified non-human animals" or "Genetically modified non-human animals" refer to animals that are heterozygous or homozygous for heterologous nucleic acids and / or genes, and / or animals that have a single copy number or multiple copy numbers of heterologous nucleic acids and / or genes. Vector: As used herein, refers to a nucleic acid molecule capable of delivering another nucleic acid to a subject to which it is bound. In some embodiments, a vector is capable of extrachromosomal replication and / or expression of a nucleic acid, allowing it to be linked to a host cell (e.g., a eukaryotic and / or prokaryotic cell). A vector capable of directing expression of an operatively linked gene is referred to herein as a " Expression carrier." Wild type: As used herein, refers to a A polypeptide is an entity with the structure and / or activity found in nature in a "normal" state or content (as opposed to mutant, diseased, altered, etc.). One of ordinary skill in the art will understand that wild-type genes and polypeptides typically exist in multiple different forms (e.g., alleles). The drawings included herein consist of the following figures and are for illustration purposes only and not for limitation. 1A and 1B show an exemplary embodiment, not to scale, of the construction strategy (described in Example 1.1) for producing a targeting vector for one embodiment of the present invention in rodents. Figure 2A shows an illustrative embodiment, not drawn to scale, of the insertion of a targeting vector (described in Example 1.1) into an engineered Igκ light chain locus in a rodent embryonic stem (ES) cell clone used to generate one embodiment of the present invention. FIG2B shows a schematic diagram of an exemplary embodiment of recombinase-mediated removal of the selection cassette (by insertion of the targeting vector (described in Example 1.1)) in an engineered Igκ light chain locus, not drawn to scale, for generating rodents of the present invention. FIG3 shows an exemplary embodiment, not drawn to scale, of the construction strategy (described in Example 1.2) used to generate a targeting vector for one embodiment of the rodent invention. Figure 4A shows a schematic diagram, not drawn to scale, illustrating the insertion of a targeting vector (described in Example 1.2) into an engineered Ig kappa light chain locus in a rodent embryonic stem (ES) cell clone used to generate the rodents of the present invention. FIG4B is a schematic diagram of an exemplary embodiment, not drawn to scale, showing the recombinase-mediated removal of the selection cassette (described in Example 1.2) in an engineered Igκ light chain locus by insertion of a targeting vector for generating rodent embodiments of the present invention. FIG5 shows the results obtained in a representative embodiment of the present invention, showing representative single cell-gate bone marrow obtained from wild-type (WT) and 6558 HO (LiK, homozygous) mice. The top row shows the expression of CD19 (y-axis) and CD3 (x-axis), and the bottom row shows the expression of CD19 with immunoglobulin D (IgD, y-axis) and immunoglobulin M (IgM, x-axis). + -Gate spleen cells. Figure 6 shows the results obtained from representative examples of the present invention, including representative single cell-gate bone marrow obtained from wild-type (WT) and 6558HO (LiK, homozygous) mice, the top row showing the expression of CD19 (y-axis) and CD3 (x-axis), and the bottom row showing the expression of immunoglobulin M (IgD, y-axis) and B220 (x-axis). FIG7 shows the results obtained from representative examples of the present invention, including representative CD19 from wild-type (WT) and 6558HO (LiK, homozygous) mice. + -Gate splenocytes illustrating the expression of immunoglobulin light chains containing mouse Igλ (y-axis) or mouse Igκ (x-axis) constant regions. Figure 8 shows the results obtained from representative examples of the present invention, including representative single cell-gate splenocytes obtained from various humanized mice, illustrating the expression of CD19 (y-axis) and CD3 (x-axis). - / - Mouse - a humanized immunoglobulin heavy chain homozygous mouse (see, e.g., U.S. Patent Nos. 8,642,835 and 8,697,940), homozygous for the LiK locus and homozygous for an inactivated endogenous immunoglobulin lambda light chain locus; and HOH / KoK / LiK / λ - / - Mouse - a humanized immunoglobulin heavy chain homozygous mouse (see, e.g., U.S. Patent Nos. 8,642,835 and 8,697,940) that is hemizygous for a kappa locus comprising the LiK locus and a second κ locus comprising a humanized immunoglobulin κ light chain locus, and is homozygous for an inactivated endogenous immunoglobulin λ light chain locus; HOH / KoK mouse - a control mouse that is homozygous for a humanized immunoglobulin heavy chain and is homozygous for a humanized immunoglobulin κ light chain. FIG9 shows the results obtained from representative examples of the present invention, including representative CD19 from various designated humanized mice. +- Gate splenocytes illustrating the expression of immunoglobulin light chains containing mouse Igλ (y-axis) or mouse Igκ (x-axis) constant regions. Figure 10 shows results obtained from representative examples of the present invention, including representative single cell-gate bone marrow obtained from various indicated humanized mice, illustrating the expression of immunoglobulin M (IgD, y-axis) and B220 (x-axis). Figure 11 shows the results obtained from representative examples of the present invention, including representative single cell-gate bone marrow obtained from various indicated humanized mice, illustrating the expression of immunoglobulin light chains containing mouse Igλ (y-axis) or mouse Igκ (x-axis) constant regions in immature (top row) and mature (bottom row) B cells. Figure 12 is a schematic diagram of an exemplary embodiment of the present invention, which is not drawn to scale, showing the engineered immunoglobulin kappa light chain locus and the rearranged locus described herein to form an mRNA molecule. Figure 13 shows the results of representative examples of the present invention, including representative SDS-PAGE protein immunoblots (Western blots) using sera isolated from wild-type (WT) and 6558 homozygous (LiK HO) mice, as described in Example 3.3. Figure 14 shows the test results of an embodiment of the present invention, showing the expression of CD19 (y-axis) and CD3 (x-axis) in a representative single cell-gate splenocyte obtained from a humanized mouse. - / - HOH / KoK / LiK / λ mouse - a humanized immunoglobulin heavy chain homozygous mouse (see, e.g., U.S. Patent Nos. 8,642,835 and 8,697,940) that is homozygous for the LiK locus and for an inactivated endogenous immunoglobulin lambda light chain locus, and includes a nucleic acid sequence encoding exogenous terminal deoxynucleotidyl transferase (TdT); and HOH / KoK / LiK / λ - / - / TdT mouse - a humanized immunoglobulin heavy chain homozygous mouse (see, e.g., U.S. Patent Nos. 8,642,835 and 8,697,940) that is hemizygous for a kappa locus comprising the LiK locus and a second κ locus comprising a humanized immunoglobulin κ light chain locus, and is homozygous for an inactivated endogenous immunoglobulin λ light chain locus that includes a nucleic acid sequence encoding exogenous terminal deoxynucleotidyl transferase (TdT). FIG15 shows the test results of the embodiment of the present invention, showing representative CD19 obtained from various designated humanized mice +- Gated splenocytes illustrating the expression of immunoglobulin light chains containing the constant regions of mouse Igλ (y-axis) or mouse Igκ (x-axis). FIG. 16 shows the test results of an embodiment of the present invention, showing representative single cell-gate bone marrow obtained from various designated humanized mice, illustrating the expression of immunoglobulin M (IgM, y-axis) and B220 (x-axis). FIG17 shows the results of testing according to an embodiment of the present invention, showing representative single cell-gate bone marrow samples obtained from various designated humanized mice, illustrating the expression of immunoglobulin light chains containing mouse Igλ (y-axis) or mouse Igκ (x-axis) in immature (top row) and mature (bottom row) B cells. FIG. 18 shows the test results of an embodiment of the present invention, showing a comparison of the immune responses of LiK / VI-3, LiK / VI-3 / TdT and VI-3 / TdT mouse strains after immunization with protein immunogens. FIG19 shows the test results of an embodiment of the present invention, showing a comparison of the immune response to the His tag in the LiK / VI-3, LiK / VI-3 / TdT and VI-3 / TdT mouse strains after immunization with an unrelated protein antigen fused to the His tag. Figure 20 shows a diagram of a portion of the endogenous human immunoglobulin lambda light chain locus, not drawn to scale. Figure 20 includes a first arrow pointing to a representative of a first exemplary endogenous human Vλ non-coding sequence in the endogenous human immunoglobulin lambda light chain locus. As shown, the first exemplary endogenous human Vλ non-coding sequence (represented by a line) in the endogenous human immunoglobulin lambda light chain locus naturally occurs near the human Vλ3-12 gene segment (represented by a dark gray square) and the human Vλ2-11 gene segment (represented by a dark gray square) in the endogenous human immunoglobulin lambda light chain locus. Figure 20 also includes a second arrow pointing to a representative of a second exemplary endogenous human Vλ coding sequence in the endogenous human immunoglobulin lambda light chain locus. As shown in the figure, a second exemplary endogenous human Vλ non-coding sequence (represented by a line) in the endogenous human immunoglobulin λ light chain locus naturally occurs near the human Vλ2-11 gene segment (represented by a dark gray square) and near the human Vλ3-10 gene segment (represented by a dark gray square) in the endogenous human immunoglobulin λ light chain locus. Figure 21 shows a diagram of a portion of the endogenous human immunoglobulin κ light chain locus, not drawn to scale. Figure 21 includes a first arrow pointing to a representative of a first exemplary endogenous human Jκ non-coding sequence of the endogenous human immunoglobulin κ light chain locus. As shown, the first exemplary endogenous human Jκ non-coding sequence (represented by a line) in the endogenous human immunoglobulin κ light chain locus naturally occurs near the human Jκ1 gene segment (represented by a dark gray square) and near the human Jκ2 gene segment (represented by a dark gray square) of the endogenous human immunoglobulin κ light chain locus. Figure 21 also includes a second arrow pointing to a representative of a second exemplary endogenous human Jκ non-coding sequence in the endogenous human immunoglobulin κ light chain locus. As shown, a second exemplary endogenous human Jκ non-coding sequence (represented by a line) in the endogenous human immunoglobulin κ light chain locus naturally occurs near the human Jκ2 gene segment (represented by a dark grey square) and near the human Jκ3 gene segment (represented by a dark grey square) of the endogenous human immunoglobulin κ light chain locus. The present invention provides a modified non-human animal having heterologous genetic material encoding a human Vλ domain, wherein the heterologous genetic material comprises human Vλ and Jλ gene sequences (i.e., gene segments) and other human sequences that provide for appropriate rearrangement (e.g., a recombination signal sequence (RSS)), and expresses antibodies having Igλ light chains, including both human and non-human portions, or antibodies having fully human Igλ light chains. For example, in various embodiments, when human gene segments are present in the genome of the modified non-human animal, corresponding recombination signal sequences may also be present (e.g., Vλ RSS and Vλ gene segments, Jλ RSS and Jλ gene segments, Vκ RSS and Vκ gene segments, Jκ RSS and Jκ gene segments, etc.). In various embodiments, the provided modified non-human animals contain heterologous genetic material inserted in such a manner that antibodies containing light chains having human Vλ domains and non-human or human Cλ domains are expressed in the non-human animal's antibody repertoire. Furthermore, provided are engineered non-human animals that contain heterologous genetic material inserted in such a manner that antibodies containing light chains having human Vλ domains and non-human or human Cλ domains are expressed from an engineered Igκ light chain locus comprising human and non-human Igλ gene sequences (e.g., gene segments), and in some embodiments, human Igκ light chain sequences are expressed in the non-human animal's germline genome. Without wishing to be bound by any particular theory, it is contemplated that the non-human animals described herein may provide an improved in vivo system for producing therapeutic antibodies utilizing antibodies expressing human Vλ domains. In some embodiments, the non-human animals described herein may also provide an alternative engineered light chain locus (e.g., an Igκ light chain locus) containing heterologous genetic material for the development of human antibody-based therapeutics (e.g., human monoclonal antibodies, multispecific binding agents, scFvs, fusion polypeptides, etc.) for disease targets associated with skewed antibody responses (e.g., antibody responses characterized by a predominance of kappa or lambda light chains). Thus, the provided non-human animals are particularly suitable for the development of human antibodies and human antibody-based molecules (e.g., multispecific binding agents, scFvs, fusion polypeptides, etc.) against targets associated with poor immunogenicity (e.g., viruses), in part due to skewed antibody repertoires and / or responses. The present invention specifically describes an immunoglobulin kappa light chain locus comprising one or more human Vλ gene segments, one or more human Jλ gene segments, and a Cλ gene. This locus is referred to as the "lambda in kappa" locus or "LiK." In particular, the present disclosure describes the generation of a non-human animal (e.g., a rodent) having a germline genome comprising a modified Igκ light chain locus, characterized in some embodiments by the introduction of a plurality of human Vλ and Jλ gene segments, and the introduction of a non-human or human Cλ gene, positioned at the non-human Cλ gene, such that the plurality of human Vλ and Jλ gene segments are operably linked to the non-human or human Cλ gene. As described herein, the generation of such a modified Igκ light chain locus results in the expression of antibodies comprising a light chain comprising a human Vλ domain and a non-human or human Cλ domain from the modified Igκ light chain locus in the non-human animal's germline genome. In some embodiments, the non-human animal provided herein comprises a germline genome comprising an Igκ light chain locus comprising a human Igλ light chain sequence. In some embodiments, the non-human animal provided has a germline genome comprising (i) an Igκ light chain locus comprising a human Igλ light chain sequence, and (ii) (a) an Igκ light chain locus comprising a human Igλ light chain sequence, or (ii) (b) an Igκ light chain locus comprising a human Igκ light chain sequence. In some embodiments, the non-human animal provided has a germline genome comprising an Igκ light chain locus as described herein, and further comprises (i) a humanized IgH locus, or (ii) a humanized IgH locus and a non-functional endogenous Igλ light chain locus that is functionally silenced or otherwise provided. As described herein, the non-human animals provided can express an antibody repertoire comprising Igλ light chains comprising human Vλ domains. In some embodiments, the non-human animals as described herein contain human Igλ light chain sequences within the Igκ light chain locus. In some embodiments, the non-human animals as described herein contain human and non-human Igλ light chain sequences within the Igκ light chain locus. In some embodiments, the non-human animals as described herein contain human Igλ and human Igκ light chain sequences within the Igκ light chain locus. In some embodiments, the non-human animals as described herein contain human Igλ, human Igκ, and murine Igκ, and / or murine Igλ light chain sequences within the Igκ light chain locus. In some embodiments, the non-human animals as described herein contain human Igλ light chain sequences, non-human Igλ light chain sequences, human Igκ light chain sequences, non-human Igκ light chain sequences, or combinations thereof within the Igκ light chain locus. In many embodiments of the non-human animals as described herein, the non-human sequences are or comprise murine sequences (e.g., mouse or rat). In some embodiments, the Igκ and / or Igλ light chain sequences comprise intergenic DNA of human and / or murine origin. In some embodiments, the Igκ and / or Igλ light chain sequences comprise intergenic DNA that is engineered and based on sequences derived from human or murine sources. In some embodiments, the intergenic DNA is positioned, inserted, positioned, or engineered (e.g., Igκ intergenic DNA in an Igκ light chain locus) such that the intergenic DNA has the same immunoglobulin locus. In some embodiments, the intergenic DNA is positioned, inserted, positioned, or engineered (e.g., Igλ intergenic DNA in an Igκ light chain locus) such that the intergenic DNA has different immunoglobulin loci. In some embodiments, the non-human animals described herein contain an engineered Igκ light chain locus containing intergenic DNA that includes an Igκ light chain sequence, an Igλ light chain sequence, and / or a combination thereof. In various embodiments, the humanized immunoglobulin heavy chain locus contains at least one human V H , at least one human D H , and at least one human J H A gene segment operatively linked to a non-human immunoglobulin heavy chain constant region (e.g., an endogenous non-human immunoglobulin heavy chain constant region comprising one or more immunoglobulin heavy chain constant region genes, such as IgM, IgD, IgG, IgE, IgA, etc.), for example, a plurality of human V H 、D H and J HGene segments operably linked to non-human immunoglobulin heavy chain constant regions. In some embodiments, provided non-human animals have a germline genome comprising one or more immunoglobulin loci depicted in the accompanying figures. Such engineered non-human animals provide a source of human antibodies and human antibody fragments and provide improved in vivo systems suitable for generating human therapeutic antibodies using human Vλ sequences. As described in the Examples section below, non-human animals are provided whose genomes contain at least one human heavy chain (i.e., V H 、D H and J H ) and light chain (e.g., Vλ and Jλ at the endogenous kappa locus) variable region gene segments, such as multiple human heavy chains (i.e., V H 、D H and J H ), and light chain (e.g., Vλ and Jλ at the endogenous kappa locus) variable region gene segments, which are located at the non-human variable region gene segments at the endogenous immunoglobulin locus location and include human non-coding intergenic DNA between the human variable region gene segments. Such intergenic DNA includes, for example, promoters, leader sequences, and recombination signal sequences, which allow for proper recombination and expression of human gene segments in the variable domains of antibodies. It should be understood by those skilled in the art that non-human immunoglobulin loci also contain such non-coding intergenic DNA. After reading the present invention, those skilled in the art will understand that other human or non-human intergenic DNA can be used to construct such loci, thereby resulting in the same expression of human variable domains in non-human animal antibodies. Such similar loci only need to contain the human coding sequences (i.e., exons) of the desired human gene segments to achieve the expression of antibodies containing human variable domains. The following sections describe various aspects of certain embodiments in detail, each of which may be applied to any aspect or embodiment described herein. The following uses are not limited. Antibody libraries from non-human animals Immunoglobulins (also known as antibodies) are large (approximately 150 kD), Y-shaped glycoproteins produced by the B cells of the host immune system to neutralize pathogens (e.g., viruses, bacteria, etc.). Each immunoglobulin (Ig) is composed of two identical heavy chains and two identical light chains, each light chain having two structural components: a variable domain and a constant domain. The heavy and light chain variable regions differ in antibodies produced by different B cells but are identical for all antibodies produced by a single B cell or B cell clone. The heavy and light chain variable regions of each antibody together comprise the antigen-binding region (or antigen-binding site). Immunoglobulins can exist as different variants, called isotypes or groups, based on the heavy chain constant region (or domain) they contain. The heavy chain constant region is identical in all antibodies of the same isotype but differs in antibodies of different isotypes. The table below summarizes nine antibody isotypes for mouse and human. Additional isotypes have been discovered in other species. Due to the different structural features between different isotypes and their discovery in different locations in the animal body (cells, tissues, etc.), the isotype confers specific biological properties to the antibody. Initially, B cells produce IgM and IgD with identical antigen-binding regions. Upon activation, B cells switch to different isotypes through a process called population switching, which involves changes in the constant regions of the antibodies produced by the B cell, while the variable regions remain the same, thus retaining the antigen specificity of the original antibody (B cell). Two separate loci (Igκ and Igλ) contain gene segments (depending on the rearrangement) that encode the light chains of antibodies and exhibit allelic and isotype exclusion. + Ratio λ +The expression ratio of B cells varies between species. For example, humans exhibit a ratio of approximately 60:40 (κ:λ). In mice and rats, a ratio of 95:5 (κ:λ) was observed. Interestingly, the κ:λ ratio observed in cats (5:95) is the opposite of that in mice and rats. Several studies have been conducted to elucidate the possible reasons behind these observed ratios, and the complexity of the locus (i.e., the number of gene segments, particularly V gene segments) and the efficiency of gene segment rearrangement have been proposed as the underlying principles. The human Igλ light chain locus extends over 1,000 kb and contains approximately 70 Vλ gene segments (29 to 33 functional) and 7 Jλ-Cλ gene segment pairs (4 to 5 functional), which are divided into three clusters (see, for example, Figure 1 of U.S. Patent No. 9,006,511, which is incorporated herein by reference in its entirety). The majority of the Vλ regions observed in the expressed antibody repertoire are encoded by gene segments contained within the most proximal cluster (referred to as cluster A). The mouse Igλ light chain locus differs significantly from the human locus, comprising only a few Vλ and Jλ gene segments, organized into two distinct gene clusters, depending on the strain (see, e.g., Figure 2 of U.S. Patent No. 9,006,511, which is incorporated herein by reference in its entirety). The development of therapeutic antibodies for the treatment of various human diseases has primarily focused on the creation of engineered non-human animal strains, particularly engineered rodent strains, that contain in their genomes varying amounts of genetic material corresponding to human immunoglobulin genes (reviewed in, e.g., Brüggemann, M. et al., 2015, Arch. Immunol. Ther. Exp. 63:101-8, which is incorporated herein by reference in its entirety). Initial efforts to create such genetically modified rodent strains focused on integrating portions of the human immunoglobulin loci that could themselves support the recombination of gene segments and the production of complete human heavy and / or light chains, while having inactivated endogenous immunoglobulin loci (see, e.g., Brüggemann, M. et al., 1989, Proc. Nat. Acad. Sci. USA 86:67-09-13; Brüggemann, M. et al., 1991, Eur. J. Immunol. 21:1323-6; Taylor, L.D. et al., 1992, Nucl. Acids Res. 20:6287-6295; Davies, N.P. et al., 1993, Biotechnol. 11:911-4; Green, L.L. et al., 1994, Nat. Genet. 7:13-21; Lonberg, N. et al., 1994, Nature 368:856-9; Taylor, LD et al., 1994, Int. Immunol. 6:579-91; Wagner, SD et al., 1994, Eur. J. Immunol. 24:2672-81; Fishwild, DM et al., 1996, Nat. Biotechnol. 14:845-51; Wagner, SD et al., 1996, Genomics 35:405-14; Mendez, MJ et al., 1997, Nat. Genet. 15:146-56; Green, LL et al., 1998, J. Exp. Med. 188:483-95; Xian, J. et al., 1998, Transgenics 2:333-43; Little, M. et al., 2000, Immunol. Today 21:364-70; Kellermann, SA and LL Green, 2002, Cur. Opin. Biotechnol. 13:593-7, which are herein incorporated by reference in their entirety).In particular, some efforts have involved integrating human Igλ light chain sequences (see, e.g., U.S. Patent Application Publication Nos. 2002 / 0088016 A1, 2003 / 0217373 A1, and 2011 / 0236378 A1; U.S. Patent Nos. 6,998,514 and 7,435,871; Nicholson, IC et al., 1999, J. Immunol. 163: 6898-906; Popov, AV et al., 1999, J. Exp. Med. 189(10): 1611-19, which are incorporated herein by reference in their entireties). These efforts have focused on random integration of yeast artificial chromosomes containing human Vλ, Jλ, and Cλ sequences, thereby creating mouse strains that express complete human Igλ light chains (i.e., human Vλ and Cλ domains). Recent efforts have employed a similar strategy using constructs that also comprise human Vλ, Jλ, and Cλ sequences (Osborn, MJ et al., 2013, J. Immunol. 190: 1481-90; Lee, EC. et al., 2014, Nat. Biotech. 32(4): 356-63, each of which is herein incorporated by reference in its entirety). However, other efforts have included specifically inserting human Vλ and Jλ gene segments into the endogenous rodent Ig light chain loci (κ and λ), such that the human Vλ and Jλ gene segments are operably linked to endogenous Ig light chain constant region genes (see, e.g., U.S. Patent Nos. 9,006,511, 9,012,717, 9,029,628, 9,035,128, 9,066,502, 9,150,662, and 9,163,092; all of which are incorporated herein by reference in their entireties). In such animals, all human Vλ gene segments from clusters A and B, as well as one or four human Jλ gene segments, are inserted into the endogenous Igκ and Igλ light chain loci. As a result, several different human Vλ and Jλ gene segments were appropriately rearranged at both engineered rodent Ig light chain loci to form functional light chains represented in the rodent antibody repertoire, comprising human Vλ domains within the context of endogenous Cκ and Cλ regions (see, e.g., Table 7 and Figures 11-13 of U.S. Patent No. 9,006,511, which is incorporated herein by reference in its entirety). Specifically, mice harboring engineered Igκ light chain loci comprising human Vλ and Jλ gene segments exhibited a human λ to endogenous λ ratio (measured by the IgCκ to IgCλ ratio) of approximately 1:1 in the spleen compartment (see, e.g., Table 4 of U.S. Patent No. 9,006,511, which is incorporated herein by reference in its entirety). Indeed, both engineered mouse strains (i.e., engineered Igκ or engineered Igλ light chain loci) demonstrated that human Vλ domains can be expressed by the rodent's endogenous Ig light chain locus, which typically exhibits significant deviations in light chain expression (see above). The present disclosure provides the understanding that an alternative engineered Ig light chain locus architecture can be generated to maximize the use of human Vλ and Jλ gene segments in the antibody repertoire for therapeutic targets in non-human animals, particularly those lacking the complexity and robust qualities typically associated with human Igλ light chain loci (i.e., such loci present in human cells) compared to non-human animals containing Igλ light chain loci (e.g., mouse and rat). This alternative engineered Ig light chain locus architecture provides the ability to generate a unique antibody repertoire by its design. The present invention demonstrates the successful production of non-human animals whose germline genomes contain an engineered endogenous Igκ light chain locus comprising a plurality of human Vλ and Jλ gene segments operably linked to non-human or human Igλ light chain constant region genes, wherein the non-human or human Igλ light chain constant region genes are inserted into the non-human Igκ light chain constant region gene position of the endogenous Igκ light chain locus. In particular, the present invention specifically demonstrates the successful production of (1) engineered non-human animals that express antibodies having human variable regions and non-human constant regions, wherein the antibodies comprise light chains comprising human Vλ domains and non-human Cλ domains, and (2) engineered non-human animals that express antibodies having human variable regions and human constant regions, wherein the antibodies comprise light chains comprising human Vλ and Cλ domains. As specifically exemplified herein, expression of such light chains is achieved by inserting the plurality of human Vλ and Jλ gene segments into the endogenous Igκ light chain locus (or alleles). In some embodiments, provided non-human animals are engineered to inactivate expression of endogenous Ig lambda light chain variable regions (eg, via gene deletion). In some embodiments, provided non-human animals are engineered to inactivate expression of endogenous Igκ light chain variable regions (e.g., by replacement or substitution). In some embodiments, provided non-human animals are engineered to express human Igλ light chain variable regions from an engineered endogenous Igκ light chain locus, as well as Igκ light chain variable regions from an engineered endogenous human Igκ light chain locus. Thus, in at least some embodiments, the present invention encompasses the development of improved in vivo systems for generating human antibodies by providing engineered non-human animals containing another engineered Igκ light chain locus that can express an antibody repertoire comprising human Vλ domains and non-human or human Cλ domains. Nucleic acid constructs Typically, a polynucleotide molecule containing a human Igλ light chain sequence (e.g., human Vλ and Jλ gene segments) or a portion thereof is linked to (e.g., inserted into) a vector, preferably a DNA vector, for replicating the polynucleotide molecule in a host cell. Human Igλ light chain sequences can be directly cloned from known sequences or sources (e.g., gene banks), or synthesized based on published sequences from GenBank or other publicly available databases (e.g., IMGT), using Computer-designed germline sequences. In addition, bacterial artificial chromosome (BAC) libraries can provide immunoglobulin DNA sequences of interest (e.g., human Vλ and Jλ sequences and combinations thereof). BAC libraries can contain inserts of 100-150 kb and can contain inserts as large as 300 kb (Shizuya, et al., 1992, Proc. Natl. Acad. Sci., USA 89: 8794-8797; Swiatek, et al., 1993, Genes and Development 7: 2071-2084; Kim, et al., 1996, Genomics 34: 213-218; herein incorporated by reference in their entireties). For example, human BAC libraries with an average insert size of 164-196 kb have been described (Osoegawa, K. et al., 2001, Genome Res. 11(3):483-96; Osoegawa, K. et al., 1998, Genomics 52:1-8, Article No. GE985423, which are incorporated herein by reference in their entireties). Human and mouse genomic BAC libraries have been constructed and are commercially available (e.g., ThermoFisher). Genomic BAC libraries can also serve as a source of immunoglobulin DNA sequences and transcriptional control regions. In addition, immunoglobulin DNA sequences can be isolated, replicated, and / or transferred from yeast artificial chromosomes (YACs). For example, the nucleotide sequence of the human Ig λ light chain locus has been determined (see, e.g., Dunham, I. et al., 1999, Nature 402:489-95, which is incorporated herein by reference in its entirety). In addition, YACs have previously been used to assemble human Ig λ light chain locus transgenes (see, e.g., Popov, AV et al., 1996, Gene 177:195-201; Popov, AV et al., 1999, J. Exp. Med. 189(10):1611-19, which are incorporated herein by reference in their entirety). The entire Ig λ light chain locus (human or rodent) can be replicated and contained in multiple YACs. If multiple YACs are used and contain overlapping regions of similarity, they can be recombined within a yeast host strain to produce a single construct representing the entire locus or a necessary portion of the locus (e.g., a region targeted by a targeting vector). The YAC arms can be additionally modified by engineering with a mammalian selection cassette to facilitate introduction of the construct into embryonic stem cells or embryos by methods known in the art and / or described herein. DNA and amino acid sequences of human Igλ light chain gene segments used to construct the engineered Igκ light chain loci described herein can be obtained from publicly available databases (e.g., GenBank, IMGT, etc.) and / or publicly available antibody sequences. In some embodiments, nucleic acid constructs containing human Igλ light chain gene segments comprise a J region (i.e., a genomic sequence comprising multiple light chain J gene segments), wherein the J region comprises the coding sequence of a human Jλ gene segment and its corresponding 12RSS, wherein the 12RSS is located within non-coding intergenic DNA, typically associated with the coding sequence of a human Jκ gene segment and its corresponding 23RSS. In some embodiments, such a sequence may be referred to as an engineered light chain J region. In some embodiments, a nucleic acid construct containing a human Igλ light chain gene segment comprises human Vλ and Jλ sequences operably linked to a human or non-human Igλ light chain constant region (Cλ) gene. In some embodiments, a nucleic acid construct containing a human Igλ light chain gene segment comprises human Vλ and Jλ sequences operably linked to one or more non-human Igκ light chain enhancer regions (or enhancer sequences). In some embodiments, a nucleic acid construct containing a human Igλ light chain gene segment comprises human Vλ and Jλ sequences operably linked to a non-human or human Cλ region gene and a non-human Igκ light chain enhancer region (or enhancer sequence). In some embodiments, the nucleic acid construct comprising human Vλ and Jλ sequences further comprises intergenic DNA of human and / or murine origin. In some embodiments, the intergenic DNA is or comprises a non-coding murine Igκ light chain sequence, a non-coding human Igκ light chain sequence, a non-coding murine Igλ light chain sequence, a non-coding human Igλ light chain sequence, or a combination thereof. Nucleic acid constructs can be prepared using methods known in the art. For example, nucleic acid constructs can be prepared as part of a larger plastid. Such preparation allows for replication and screening of the correct construct in an efficient manner known in the art. As described herein, a nucleic acid construct (in whole or in part) containing a human Ig lambda light chain sequence can be positioned between restriction sites on the plastid, allowing it to be separated from the remaining plastid sequence for incorporation into the desired non-human animal. Various methods for preparing nucleic acid constructs (e.g., plastids) and transforming host organisms are known in the art. For other suitable expression systems for prokaryotes and eukaryotic cells, as well as general recombination procedures, see Principles of Gene Manipulation: An Introduction to Genetic Manipulation, Fifth Edition, Old, RW and SB Primrose, eds., Blackwell Science, Inc., 1994 and Molecular Cloning: A Laboratory Manual, Second Edition, Sambrook, J. et al., eds., Cold Spring Harbor Laboratory Press: 1989, each of which is incorporated herein by reference in its entirety. Targeting vector Targeting vectors can be used to introduce a nucleic acid construct into a genomic target locus and comprise a nucleic acid construct and homology arms flanking the nucleic acid construct; those skilled in the art will understand the various options and features generally applicable to the design, structure and / or use of targeting vectors. For example, the targeting vector can be in linear or circular form, and it can be single-stranded or double-stranded. The targeting vector can be deoxyribonucleic acid (DNA) or ribonucleic acid (RNA). For ease of reference, the homology arms are referred to herein as 5' and 3' (i.e., upstream and downstream) homology arms. The terms refer to the relative positions of the homology arms to the nucleic acid construct within the targeting vector. The 5' and 3' homology arms correspond to regions within the targeted locus, or regions within another targeting vector, which are referred to herein as " 5' target sequence" and" In some embodiments, the homology arm can also serve as the 5' or 3' target sequence. In some embodiments, the methods described herein utilize two, three, or more targeting vectors capable of recombination with one another. In various embodiments, the targeting vector is a large targeting vector (LTVEC) as described elsewhere herein. In such embodiments, each of the first, second, and third targeting vectors comprises a 5' and a 3' homology arm. The 3' homology arm of the first targeting vector comprises a sequence that overlaps (i.e., an overlapping sequence) with the 5' homology arm of the second targeting vector, which allows homologous recombination between the first and second LTVECs. In a dual-targeting approach, the 5' homology arm of the first targeting vector and the 3' homology arm of the second targeting vector can be similar to corresponding fragments within the target genomic locus (i.e., target sequence), which can promote homologous recombination between the first and second targeting vectors and the corresponding genomic fragments and modify the target genomic locus. In the triple targeting method, the 3' homology arm of the second targeting vector may contain a sequence that overlaps with the 5' homology arm of the third targeting vector (i.e., an overlapping sequence), which can allow homologous recombination between the second and third LTVECs. The 5' homology arm of the first targeting vector and the 3' homology arm of the third targeting vector are similar to the corresponding fragments (i.e., target sequences) within the target genomic locus, which can promote the homologous recombination of the first and third targeting vectors with the corresponding genomic fragments and modify the target genomic locus. Homology arm and target sequence or two homology arms" Correspond" or " When the two regions share sufficient sequence identity with each other, the other serves as the recipient for the homologous recombination reaction. The degree of sequence identity between a particular target sequence found on a targeting vector (i.e., overlapping sequence) or between two homology arms and the corresponding homology arms can be any degree of sequence identity that allows homologous recombination to occur. By way of example only, the degree of sequence identity shared by a homology arm of a targeting vector (or a fragment thereof) and a target sequence of another targeting vector, or a target sequence of a target genomic locus (or a fragment thereof) can be, for example, but not limited to, at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to allow the sequences to undergo homologous recombination. Furthermore, the corresponding regions of similarity (eg, identity) between the homology arms and the corresponding target sequences can be of any length sufficient to promote homologous recombination at the target genomic locus. For example, a particular homology arm and / or corresponding target sequence can comprise a corresponding region of similarity, such as, but not limited to, about 5-10 kb, 5-15 kb, 5-20 kb, 5-25 kb, 5-30 kb, 5-35 kb, 5-40 kb, 5-45 kb, 5-50 kb, 5-55 kb, 5-60 kb, 5-65 kb, 5-70 kb, 5-75 kb, 5-80 kb, 5-85 kb, 5-90 kb, 5-95 kb, 5-100 kb, 100-200 kb, or 200-300 kb in length (e.g., as described elsewhere herein), such that the homology arms have sufficient similarity to allow homologous recombination with a corresponding target sequence within a target genomic locus in a cell or within another targeting vector. In some embodiments, a particular homology arm and / or corresponding target sequence may comprise a corresponding region of similarity, for example, but not limited to, about 10-100 kb, 15-100 kb, 20-100 kb, 25-100 kb, 30-100 kb, 35-100 kb, 40-100 kb, 45-100 kb, 50-100 kb, 55-100 kb, 60-100 kb, 65-100 kb, 70-100 kb, 75-100 kb, 80-100 kb, 85-100 kb, 90-100 kb, or 95-100 kb in length (e.g., as described elsewhere herein), such that the homology arms have sufficient similarity to allow homologous recombination with the corresponding target sequence within the target genomic locus of the cell or within another targeting vector. The overlapping sequence of the 3' homology arm of the first targeting vector and the 5' homology arm of the second targeting vector, or the overlapping sequence of the 3' homology arm of the second targeting vector and the 5' homology arm of the third targeting vector, can be of any length sufficient to promote homologous recombination between the targeting vectors. For example, the specific overlapping sequences of the homology arms can include corresponding overlapping regions that are about 1-5 kb, 5-10 kb, 5-15 kb, 5-20 kb, 5-25 kb, 5-30 kb, 5-35 kb, 5-40 kb, 5-45 kb, 5-50 kb, 5-55 kb, 5-60 kb, 5-65 kb, 5-70 kb, 5-75 kb, 5-80 kb, 5-85 kb, 5-90 kb, 5-95 kb, 5-100 kb, 100-200 kb, or 200-300 kb in length such that the homology arms have sufficient similarity to allow homologous recombination with corresponding target sequences within the target genomic locus of the cell or within another targeting vector. In some embodiments, a particular homology arm and / or corresponding target sequence may comprise a corresponding region of similarity, for example, but not limited to, 1-100 kb, 5-100 kb, 10-100 kb, 15-100 kb, 20-100 kb, 25-100 kb, 30-100 kb, 35-100 kb, 40-100 kb, 45-100 kb, 50-100 kb, 55-100 kb, 60-100 kb, 65-100 kb, 70-100 kb, 75-100 kb, 80-100 kb, 85-100 kb, 90-100 kb, or 95-100 kb in length, such that the homology arms have sufficient similarity to allow homologous recombination with the corresponding target sequence within the target genomic locus of the cell or within another targeting vector. In some embodiments, the overlapping sequence is 1-5 kb, inclusive. In some embodiments, the overlapping sequence is about 1 kb to about 70 kb, inclusive. In some embodiments, the overlapping sequence is about 10 kb to about 70 kb, inclusive. In some embodiments, the overlapping sequence is about 10 kb to about 50 kb, inclusive. In some embodiments, the overlapping sequence is at least 10 kb. In some embodiments, the overlapping sequence is at least 20 kb. For example, the overlapping sequence can be about 1 kb to about 5 kb, inclusive, about 5 kb to about 10 kb, inclusive, about 10 kb to about 15 kb, inclusive, about 15 kb to about 20 kb, inclusive, about 20 kb to about 25 kb, inclusive.Inclusive, about 25kb to about 30kb, inclusive, about 30kb to about 35kb, inclusive, about 35kb to about 40kb, inclusive, about 40kb to about 45kb, inclusive, about 45kb to about 50kb, inclusive, about 50kb to about 60kb, inclusive, about 60kb to about 70kb, inclusive, about 70kb to about 80kb, inclusive, about 80kb to about 90kb, inclusive, about 90kb to about 100kb, inclusive, about 100kb to about kb, about 120 kb, inclusive, about 120 kb to about 140 kb, inclusive, about 140 kb to about 160 kb, inclusive, about 160 kb to about 180 kb, inclusive, about 180 kb to about 200 kb, inclusive, about 200 kb to about 220 kb, inclusive, about 220 kb to about 240 kb, inclusive, about 240 kb to about 260 kb, inclusive, about 260 kb to about 280 kb, inclusive, or about 280 kb to about 300 kb, inclusive. By way of example only, overlapping sequences can be from about 20 kb to about 60 kb, inclusive. Furthermore, the overlapping sequence can be at least 1 kb, at least 5 kb, at least 10 kb, at least 15 kb, at least 20 kb, at least 25 kb, at least 30 kb, at least 35 kb, at least 40 kb, at least 45 kb, at least 50 kb, at least 60 kb, at least 70 kb, at least 80 kb, at least 90 kb, at least 100 kb, at least 120 kb, at least 140 kb, at least 160 kb, at least 180 kb, at least 200 kb, at least 220 kb, at least 240 kb, at least 260 kb, at least 280 kb, or at least 300 kb. In some embodiments, the overlapping sequence may be at most 400 kb, at most 350 kb, at most 300 kb, at most 280 kb, at most 260 kb, at most 240 kb, at most 220 kb, at most 200 kb, at most 180 kb, at most 160 kb, at most 140 kb, at most 120 kb, at most 100 kb, at most 90 kb, at most 80 kb, at most 70 kb, at most 60 kb, or at most 50 kb. In some embodiments, the homology arms can correspond to a locus (e.g., a targeting locus) that is natural to the cell, or they can correspond to heterologous or exogenous DNA fragments that are integrated into the cell genome, including, for example, transgenic, expression cassettes, or heterologous or exogenous regions of DNA. In some embodiments, the homology arms can correspond to a region on the targeting vector in the cell. In some embodiments, the homology arms of the targeting vector can correspond to yeast artificial chromosomes (YACs), bacterial artificial chromosomes (BACs), human artificial chromosomes, or any other modified region contained in appropriate host cells. In addition, the homology arms of the targeting vector can correspond to or be derived from a region of a BAC library, a cohesive plasmid library, or a P1 phage library. In some embodiments, the homology arms of the targeting vector correspond to original, heterologous, or exogenous prokaryotes, yeasts, birds (e.g., chickens), non-human mammals, rodents, humans, rats, mice, hamsters, rabbits, pigs, cattle, deer, sheep, goats, cats, dogs, ferrets, primates (e.g., marmosets, rhesus monkeys), domestic mammals, agricultural mammals, or any other organism of interest. In some embodiments, the homology arms correspond to loci in cells that show limited sensitivity for targeting using conventional methods, or show relatively low integration success at the target site, and / or significant off-target integration, in the absence of nicks or double-strand breaks induced by nuclease agents (e.g., Cas proteins). In some embodiments, the homology arms are designed to include engineered DNA. In some embodiments, the 5' and 3' homology arms of the targeting vector correspond to the target genome. Alternatively, the homology arms correspond to related genomes. For example, the target genome is a mouse genome of a first strain, and the targeting arms correspond to a mouse genome of a second strain, wherein the first strain and the second strain are different. In certain embodiments, the homology arms correspond to the genome of the same animal, or a genome from the same strain, for example, the target genome is a mouse genome of a first strain, and the targeting arms correspond to a mouse genome from the same mouse or the same strain. The homology arms of the targeting vector can be of any length sufficient to promote a homologous recombination event with the corresponding target sequence, including, for example, 1-5 kb, inclusive, 5-10 kb, inclusive, 5-15 kb, inclusive, 5-20 kb, inclusive, 5-25 kb, inclusive, 5-30 kb, inclusive, 5-35 kb, inclusive, 5-40 kb, inclusive, 5-45 kb, inclusive, 5-50 kb in length. , inclusive, 5-55kb, inclusive, 5-60kb, inclusive, 5-65kb, inclusive, 5-70kb, inclusive, 5-75kb, inclusive, 5-80kb, inclusive, 5-85kb, inclusive, 5-90kb, inclusive, 5-95kb, inclusive, 5-100kb, inclusive, 100-200kb, inclusive, or 200-300kb, inclusive. In some embodiments, the homology arms of the targeting vector can be of any length sufficient to promote homologous recombination events with the corresponding target sequence, which are 1-100 kb, inclusive, 5-100 kb, inclusive, 10-100 kb, inclusive, 15-100 kb, inclusive, 20-100 kb, inclusive, 25-100 kb, inclusive, 30-100 kb, inclusive, 35-100 kb, inclusive, 40-100 kb, inclusive, 100 kb, inclusive, 45-100 kb, inclusive, 50-100 kb, inclusive, 55-100 kb, inclusive, 60-100 kb, inclusive, 65-100 kb, inclusive, 70-100 kb, inclusive, 75-100 kb, inclusive, 80-100 kb, inclusive, 85-100 kb, inclusive, 90-100 kb, inclusive, or 95-100 kb, inclusive. As described herein, large targeting vectors can employ longer targeting arms. Nuclease reagents (e.g., CRISPR / Cas systems) can be used in combination with targeting vectors to promote modification of a target locus (e.g., modification of an Ig kappa light chain locus, or modification of a previously modified or engineered Ig kappa light chain locus). Such nuclease reagents can promote homologous recombination between the targeting vector and the target locus. When a nuclease reagent is used in combination with a targeting vector, the targeting vector can comprise 5' and 3' homology arms corresponding to 5' and 3' target sequences located sufficiently close to the nuclease cleavage site to promote homologous recombination events between the target sequence and the homology arms at the nick or double-strand break at the nuclease cleavage site. The term " A "nuclease cleavage site" includes a DNA sequence where a nick or double-strand break is created by a nuclease agent (e.g., a Cas9 cleavage site). The target sequences within the target locus corresponding to the 5' and 3' homology arms of the targeting vector are " "Sufficiently close" to a nuclease cleavage site is defined as being within a distance that facilitates homologous recombination events between the 5' and 3' target sequences and the homology arms at the nick or double-strand break at the recognition site. Thus, in certain embodiments, the target sequence corresponding to the 5' and / or 3' homology arms of the targeting vector is within at least one nucleotide of the specific recognition site, or within at least 10 nucleotides to about 14 kb of the specific recognition site. In some embodiments, the nuclease cleavage site is immediately adjacent to at least one or both of the target sequences. The spatial relationship of the target sequence corresponding to the homology arms of the targeting vector and the nuclease cleavage site can vary. For example, the target sequence can be located 5' to the nuclease cleavage site, the target sequence can be located 3' to the recognition site, or the target sequence can flank the nuclease cleavage site. The use of a targeting vector (including, for example, a large targeting vector) in combination with a nuclease agent can increase the targeting efficiency compared to the use of the targeting vector alone. For example, when the targeting vector is used in combination with the nuclease agent, the targeting efficiency of the targeting vector can be increased by at least two times, at least three times, at least four times, at least five times, at least six times, at least seven times, at least eight times, at least nine times, at least ten times, or within a range formed by these integers, such as 2-10 times, compared to the use of the targeting vector alone. Some targeting vectors are "Large targeting vectors" or "LTVECs" include targeting vectors that contain homology arms corresponding to and derived from nucleic acid sequences that are larger than those typically used for other methods of performing homologous recombination in cells. The length of an LTVEC can be, for example, at least 10 kb, or the sum of the 5' homology arm and the 3' homology arm can be, for example, at least 10 kb. LTVECs also include targeting vectors that contain nucleic acid constructs that are larger than those typically used for other methods of performing homologous recombination in cells. For example, due to the size limitations of LTVECs, LTVECs can enable modification of large loci that cannot be accommodated by traditional plastid-based targeting vectors. For example, the locus of interest can be (i.e., the 5' and 3' homology arms can correspond to) a locus in the cell that cannot be targeted using conventional methods, or that can only be targeted incorrectly, or only with significantly lower efficiency, in the absence of a nick or double-strand break induced by a nuclease agent (e.g., a Cas protein). In some embodiments, the methods described herein use two or three LTVECs that are capable of recombining with each other and with the genomic locus of interest in a three-way or four-way recombination event. These methods enable modification of large loci that would not be possible using a single LTVEC. Examples of LTVECs include vectors derived from bacterial artificial chromosomes (BACs), artificial human chromosomes, or yeast artificial chromosomes (YACs). LTVECs can be in linear or circular form. Examples of LTVECs and methods for making them are described, for example, in U.S. Patent Nos. 6,586,251, 6,596,541, and 7,105,348; International Patent Application Publication No. WO 2002 / 036789, each of which is incorporated herein by reference in its entirety. Provide non-human animals, cells and tissues. Non-human animals are provided that express (e.g., express by their B cells) antibodies comprising a light chain comprising a human Vλ domain generated by the integration of genetic material corresponding to at least a portion of a human Igλ light chain locus (i.e., at least a portion of a human Vλ and Jλ gene segment), and encoding a human Vλ domain (i.e., a rearranged human Vλ-Jλ sequence) located at the corresponding non-human Igκ light chain variable region sequence in the genome of the non-human animal's germline. Suitable examples as described herein include, but are not limited to, rodents, particularly mice. The present invention provides an improved in vivo system for identifying and developing new antibodies, antibody components (e.g., antigen-binding portions, and / or compositions or formats comprising the same), and / or antibody-based therapeutics, for example, for treating various diseases affecting humans. Furthermore, the present invention also includes non-human animals (e.g., rodents) that can be identified that have engineered immunoglobulin loci, such as engineered immunoglobulin (Ig) kappa (κ) light chain loci, and / or that otherwise express, produce, or contain antibody repertoires characterized by light chain (λ) regions having human Vλ. For example, in some embodiments, such non-human animals can be used to identify and develop novel antibody-based therapeutics by exploiting the diversity of human Vλ sequences. In some embodiments, the non-human animals described herein provide improved in vivo systems for developing antibodies and / or antibody-based therapeutics for human administration. In some embodiments, the non-human animals described herein provide an improved in vivo system for developing antibodies and / or antibody-based therapeutics for human administration comprising human Vλ domains characterized by enhanced expression (e.g., expression and / or presentation in an antigen-specific antibody repertoire) compared to antibodies and / or antibody-based therapeutics obtained using existing in vivo systems that contain human Vλ region sequences. The present invention particularly provides non-human animals having an Igκ light chain locus comprising a modified immunoglobulin light chain variable region and a modified immunoglobulin light chain constant region gene. As described herein, the non-human animals provided herein contain in their germline genome an immunoglobulin κ light chain locus comprising a modified immunoglobulin κ light chain variable region characterized by the presence of one or more human Vλ gene segments and one or more human Jλ gene segments, wherein the one or more human Vλ and one or more human Jλ gene segments are operably linked to an immunoglobulin λ light chain constant region (Cλ) gene, wherein the immunoglobulin λ light chain constant region (Cλ) gene is located at a non-human immunoglobulin κ light chain constant region (Cκ) gene at an endogenous immunoglobulin κ locus of the non-human animal. In some embodiments, the non-human animals provided herein comprise an Igκ light chain locus comprising intergenic DNA derived from an immunoglobulin λ light chain and / or an immunoglobulin κ light chain, and combinations thereof. In many embodiments, the engineered immunoglobulin kappa light chain variable region further comprises an immunoglobulin kappa light chain sequence positioned or inserted between the one or more human Vλ gene segments and the one or more human Jλ gene segments. In some embodiments, the immunoglobulin kappa light chain sequence positioned or inserted between the one or more human Vλ gene segments and the one or more human Jλ gene segments is or comprises a murine (e.g., rat or mouse) sequence. In some embodiments, the immunoglobulin kappa light chain sequence positioned or inserted between the one or more human Vλ gene segments and the one or more human Jλ gene segments is or comprises a human sequence. For example, in some embodiments, the human immunoglobulin kappa light chain sequence is or comprises a genomic sequence that naturally occurs between the human Vκ4-1 gene segment and the human Jκ1 gene segment at the human immunoglobulin kappa light chain locus. In some embodiments, the non-human animals provided comprise at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, or at least 25 functional human νλ gene segments. In some embodiments, the non-human animals provided comprise 5 to 25, 5 to 24, 5 to 23, 5 to 22, 5 to 21, 5 to 20, 5 to 19, 5 to 18, 5 to 17, 5 to 16, 5 to 15, 5 to 14, 5 to 13, 5 to 12, 5 to 11, 5 to 10, 5 to 9, 5 to 8, 5 to 7, or 5 to 6 functional human νλ gene segments. In some embodiments, the non-human animals provided comprise 6 to 25, 7 to 25, 8 to 25, 9 to 25, 10 to 25, 11 to 25, 12 to 25, 13 to 25, 14 to 25, 15 to 25, 16 to 25, 17 to 25, 18 to 25, 19 to 25, 20 to 25, 21 to 25, 22 to 25, 23 to 25, or 24 to 25 functional human νλ gene segments. In some embodiments, the non-human animals provided comprise 6 to 24, 7 to 23, 8 to 22, 9 to 21, 10 to 20, 11 to 19, 12 to 18, 13 to 17, 14 to 16, or 15 to 16 functional human νλ gene segments. In some embodiments, a non-human animal is provided that comprises 6 to 24, 7 to 23, 8 to 22, 9 to 21, 10 to 20, 11 to 19, 12 to 18, 13 to 17, or 14 to 16 functional human Vλ gene segments. In some embodiments, provided non-human animals comprise a total of 10 to 70, 10 to 65, 10 to 60, 10 to 55, 10 to 50, 10 to 45, 10 to 40, 10 to 35, 10 to 30, 10 to 25, 10 to 20, or 10 to 15 human Vλ gene segments. In some embodiments, provided non-human animals comprise a total of 15 to 70, 20 to 70, 25 to 70, 30 to 70, 35 to 70, 40 to 70, 45 to 70, 50 to 70, 55 to 70, 60 to 70, or 65 to 70 human Vλ gene segments. In some embodiments, provided non-human animals comprise a total of 15 to 65, 20 to 60, 25 to 55, 20 to 50, 25 to 45, 30 to 40, 30 to 35, or 35 to 40 human Vλ gene segments. In some embodiments, the non-human animals provided contain human Vλ and / or Jλ gene segments in a natural or germline configuration (e.g., a DNA sequence containing multiple human Vλ and / or Jλ gene segment encoding sequences interspersed with non-encoding human immunoglobulin λ light chain sequences). In some embodiments, the non-human animals provided contain human Vλ and / or Jλ gene segments that are away from or deviate from a natural or germline configuration (e.g., a DNA sequence containing multiple human Vλ and / or Jκ gene segment encoding sequences interspersed with non-encoding immunoglobulin λ light chain sequences (e.g., human or murine). In some embodiments, the non-human animals provided contain human Vλ and / or Jλ gene segments in a configuration that does not naturally occur in the human immunoglobulin λ light chain locus of the human cell germline genome. In some embodiments, non-human animals are provided that contain a DNA sequence located at an endogenous non-human Igκ light chain locus that includes a plurality of human Vλ and Jλ coding sequences interspersed (or juxtaposed, bound, etc.) with non-coding human immunoglobulin light chain sequences (e.g., κ, λ, and combinations thereof). In some embodiments, non-human animals are provided that contain a DNA sequence located at an endogenous non-human Igλ light chain locus that includes a plurality of human Vλ and Jλ coding sequences interspersed with non-coding non-human (e.g., murine) immunoglobulin λ light chain sequences. In some embodiments, provided non-human animals are characterized by expressing an antibody derived from an endogenous immunoglobulin kappa light chain locus in the non-human animal's germline genome, the antibody comprising (1) a human Vλ domain and (2) a non-human or human Cλ domain. In some embodiments, provided non-human animals are characterized by increased utilization (e.g., but not limited to, about 2-fold) of the human Vλ region of the engineered immunoglobulin kappa light chain locus compared to one or more reference engineered non-human animals. In some embodiments, a non-human animal, non-human cell, or non-human tissue is provided whose germline genome comprises an endogenous immunoglobulin κ light chain locus comprising: (a) one or more human Vλ gene segments, (b) one or more human Jλ gene segments, and (c) a Cλ gene, wherein (a) and (b) are operably linked to (c), wherein the rodent lacks a rodent Cκ gene at the endogenous immunoglobulin κ light chain locus. In some embodiments, a non-human animal, non-human cell, or non-human tissue is provided, wherein the germline genome comprises an endogenous immunoglobulin kappa light chain locus comprising an insertion of one or more human Vλ gene segments, one or more human Jλ gene segments, and a Cλ gene, wherein the human Vλ and Jλ gene segments are operably linked to the Cλ gene, and wherein the Cλ gene is inserted at the non-human Cκ gene site of the endogenous immunoglobulin kappa light chain locus. In many embodiments of the non-human animal, non-human cell, or non-human tissue, the Cλ gene inserted at the non-human Cκ gene site of the endogenous immunoglobulin kappa light chain locus is a non-human or human Cλ gene. In some embodiments, the non-human Cλ gene is or comprises a mammalian Cλ gene selected from the group consisting of primate, goat, sheep, pig, dog, cow, or rodent Cλ genes. In some embodiments, the non-human C[lambda] gene is or comprises a rodent C[lambda] gene. In some embodiments, the rodent Cλ gene is or comprises a mouse Cλ gene. In some embodiments, the mouse Cλ gene comprises a sequence that is at least 80%, at least 85%, at least 90%, at least 95%, or at least 98% identical to a mouse Cλ gene selected from the group consisting of mouse Cλ1, mouse Cλ2, and mouse Cλ3. In some embodiments, a mouse Cλ gene comprises a sequence that is substantially identical or identical to a mouse Cλ gene selected from the group consisting of mouse Cλ1, mouse Cλ2, and mouse Cλ3. In some embodiments, the mouse Cλ1 gene is or comprises SEQ ID NO: 1. In some embodiments, the mouse Cλ2 gene is or comprises SEQ ID NO: 3. In some embodiments, the mouse Cλ3 gene is or comprises SEQ ID NO: 5. In some embodiments, the mouse Cλ gene comprises a sequence that is identical to a mouse Cλ1 gene. In some embodiments, the mouse Cλ gene comprises a sequence that is 80%-100%, 85%-100%, 90%-100%, 95%-100%, or 98%-100% identical to a mouse Cλ gene selected from the group consisting of mouse Cλ1, mouse Cλ2, and mouse Cλ3. In some embodiments, the mouse Cλ gene comprises a sequence that is at least 80%-98%, 80%-95%, 80%-90%, or 80%-85% identical to a mouse Cλ gene selected from the group consisting of mouse Cλ1, mouse Cλ2, and mouse Cλ3. In some embodiments, the mouse Cλ gene comprises a sequence that is 85%-98%, 90%-95%, or 88%-93% identical to a mouse Cλ gene selected from the group consisting of mouse Cλ1, mouse Cλ2, and mouse Cλ3. In some embodiments, the rodent Cλ gene is or comprises a rat Cλ gene. In some embodiments, the rat Cλ gene comprises a sequence that is at least 80%, at least 85%, at least 90%, at least 95%, or at least 98% identical to a rat Cλ gene selected from the group consisting of rat Cλ1, rat Cλ2, rat Cλ3, and rat Cλ4 genes. In some embodiments, the rat Cλ gene comprises a sequence that is substantially identical or identical to a rat Cλ gene selected from the group consisting of rat Cλ11, rat Cλ2, rat Cλ3, and rat Cλ4 genes. In certain embodiments, the rat Cλ1 gene is or comprises SEQ ID NO: 7. In certain embodiments, the rat Cλ2 gene is or comprises SEQ ID NO: 9. In certain embodiments, the rat Cλ3 gene is or comprises SEQ ID NO: 11. In certain embodiments, the rat Cλ4 gene is or comprises SEQ ID NO: 13. In some embodiments, the rat Cλ gene comprises a sequence that is 80% to 100%, 85% to 100%, 90% to 100%, 95% to 100%, or 98% to 100% identical to a rat Cλ gene selected from the group consisting of rat Cλ1, rat Cλ2, rat Cλ3, and rat Cλ4 genes. In some embodiments, the rat Cλ gene comprises a sequence that is 80% to 98%, 80% to 95%, 80% to 90%, or 80% to 85% identical to a rat Cλ gene selected from the group consisting of rat Cλ1, rat Cλ2, rat Cλ3, and rat Cλ4 genes. In some embodiments, the rat Cλ gene comprises a sequence that is 85% to 98%, 90% to 95%, or 88% to 93% identical to a rat Cλ gene selected from the group consisting of rat Cλ1, rat Cλ2, rat Cλ3, and rat Cλ4 genes. In some embodiments, the human Cλ gene comprises a sequence that is at least 80%, at least 85%, at least 90%, at least 95%, or at least 98% identical to a human Cλ gene selected from the group consisting of human Cλ1, human Cλ2, human Cλ3, human Cλ6, and human Cλ7 genes. In some embodiments, the human Cλ gene comprises a sequence that is substantially identical or identical to a human Cλ gene selected from the group consisting of human Cλ, human Cλ2, human Cλ3, human Cλ6, and human Cλ7 genes. In some embodiments, the human Cλ gene comprises a sequence that is identical to a human Cλ gene selected from the group consisting of human Cλ1, human Cλ2, human Cλ3, human Cλ6, and human Cλ7 genes. In certain embodiments, the human Cλ1 gene is or comprises SEQ ID NO: 15. In certain embodiments, the human Cλ2 gene is or comprises SEQ ID NO: 17. In certain embodiments, the human Cλ3 gene is or comprises SEQ ID NO: 19. In certain embodiments, the human Cλ6 gene is or comprises SEQ ID NO: 21. In certain embodiments, the human Cλ7 gene is or comprises SEQ ID NO: 23. In certain embodiments, the human Cλ gene is or comprises a human Cλ2 gene. In some embodiments, the human Cλ gene comprises a sequence that is 80% to 100%, 85% to 100%, 90% to 100%, 95% to 100%, or 98% to 100% identical to a human Cλ gene selected from the group consisting of human Cλ1, human Cλ2, human Cλ3, human Cλ6, and human Cλ7 genes. In some embodiments, the human Cλ gene comprises a sequence that is 80% to 98%, 80% to 95%, 80% to 90%, or 80% to 85% identical to a human Cλ gene selected from the group consisting of human Cλ1, human Cλ2, human Cλ3, human Cλ6, and human Cλ7 genes. In some embodiments, the human Cλ gene comprises a sequence that is 85%-98%, 90%-95%, or 88%-93% identical to a human Cλ gene selected from the group consisting of human Cλ1, human Cλ2, human Cλ3, human Cλ6, and human Cλ7 genes. In some embodiments of the provided non-human animals, non-human cells, or non-human tissues, the insertion of one or more human Vλ gene segments and one or more human Jλ gene segments replaces the non-human Vκ and Jκ gene segments at the endogenous immunoglobulin κ light chain locus. In some embodiments, the insertion comprises human non-coding DNA naturally occurring between the human Vλ and Jλ gene segments, and combinations thereof. In some embodiments of the provided non-human animals, non-human cells, or non-human tissues, the insertion of one or more human Vλ gene segments and one or more human Jλ gene segments is located within or replaces the non-human Vκ and Jκ gene segments at the endogenous immunoglobulin κ light chain locus. In some embodiments of the provided non-human animals, non-human cells, or non-human tissues, the immunoglobulin κ light chain locus comprises an insertion of at least 24, at least 34, at least 52, at least 61, or at least 70 human Vλ gene segments and at least 1, at least 2, at least 3, at least 4, or at least 5 human Jλ gene segments. In some embodiments of the non-human animals, non-human cells, or non-human tissues provided, the immunoglobulin kappa light chain locus comprises an insertion of 39 human tear Vλ gene segments and at least 5 human Jλ gene segments. In some embodiments of the non-human animals, non-human cells, or non-human tissues provided, the immunoglobulin kappa light chain locus comprises an insertion of human Vλ4-69, Vλ8-61, Vλ4-60, Vλ6-57, Vλ10-54, Vλ5-52, Vλ1-51, Vλ9-49, Vλ1-47, Vλ7-46, Vλ5-45, Vλ1-44, Vλ7-43, Vλ1-40, Vλ5-39 , Vλ5-37, Vλ1-36, Vλ3-27, Vλ3-25, Vλ2-23, Vλ3-22, Vλ3-21, Vλ3-19, Vλ3-16, Vλ2-14, Vλ3-12, Vλ2-11, Vλ3-10, Vλ3-9, Vλ2-8, Vλ4-3, Vλ3-1 or any combination thereof, and human Jλ1, Jλ2, Jλ3, Jλ6, Jλ7 or any combination thereof.In some embodiments, the insertion comprises human noncoding DNA that naturally occurs adjacent to the endogenous human lambda light chain locus at human Vλ4-69, Vλ8-61, Vλ4-60, Vλ6-57, Vλ10-54, Vλ5-52, Vλ1-51, Vλ9-49, Vλ1-47, Vλ7-46, Vλ5-45, Vλ1-44, Vλ7-43, Vλ1-40, Vλ5-39, Vλ5- or Vλ3-1, and human non-coding DNA (all or part) that naturally occurs in human Jλ1, Jλ2, Jλ3, Jλ6 or Jλ7 adjacent to the endogenous human lambda light chain locus. In some embodiments, the insertion comprises human noncoding DNA that naturally occurs adjacent to the endogenous human lambda light chain locus at human Vλ4-69, Vλ8-61, Vλ4-60, Vλ6-57, Vλ10-54, Vλ5-52, Vλ1-51, Vλ9-49, Vλ1-47, Vλ7-46, Vλ5-45, Vλ1-44, Vλ7-43, Vλ1-40, Vλ5-39, Vλ5-37, Vλ1- 36, Vλ3-27, Vλ3-25, Vλ2-23, Vλ3-22, Vλ3-21, Vλ3-19, Vλ3-16, Vλ2-14, Vλ3-12, Vλ2-11, Vλ3-10, Vλ3-9, Vλ2-8, Vλ4-3, or Vλ3-1, and human non-coding DNA that naturally occurs in human Jκ1, Jκ2, Jκ3, Jκ4, or Jκ5 adjacent to the endogenous human κ light chain locus.In some embodiments, human Vλ4-69, Vλ8-61, Vλ4-60, Vλ6-57, Vλ10-54, Vλ5-52, Vλ1-51, Vλ9-49, Vλ1-47, Vλ7-46, Vλ5-45, Vλ1-44, Vλ7-43, Vλ1-40, Vλ5-39, Vλ5-37, Vλ1-36, Vλ3-27, Vλ3-25, Vλ2 Insertions of Vλ3-1, Vλ3-23, Vλ3-22, Vλ3-21, Vλ3-19, Vλ3-16, Vλ2-14, Vλ3-12, Vλ2-11, Vλ3-10, Vλ3-9, Vλ2-8, Vλ4-3, Vλ3-1, or any combination thereof, comprise human non-coding DNA naturally occurring adjacent to the endogenous human lambda light chain locus at human Vλ4-69, Vλ8-61, Vλ4-60, Vλ6-57, Vλ10-54, Vλ5-52, Vλ1-51, Vλ9-49, Vλ1-47, Vλ7-46, Vλ5-45, Vλ1-44, Vλ7-43, Vλ1 -40, Vλ5-39, Vλ5-37, Vλ1-36, Vλ3-27, Vλ3-25, Vλ2-23, Vλ3-22, Vλ3-21, Vλ3-19, Vλ3-16, Vλ2-14, Vλ3-12, Vλ2-11, Vλ3-10, Vλ3-9, Vλ2-8, Vλ4-3, or Vλ3-1, and an insertion of human Jλ1, Jλ2, Jλ3, Jλ6, Jλ7, or any combination thereof, including human non-coding DNA (in whole or in part) that naturally occurs in human Jλ1, Jλ2, Jλ3, Jλ6, Jλ7 adjacent to the endogenous human lambda light chain locus.In some embodiments, human Vλ4-69, Vλ8-61, Vλ4-60, Vλ6-57, Vλ10-54, Vλ5-52, Vλ1-51, Vλ9-49, Vλ1-47, Vλ7-46, Vλ5-45, Vλ1-44, Vλ7-43, Vλ1-40, Vλ5-39, Vλ5-37, Vλ1-36, Vλ3-27, Vλ3-25, Vλ2- 23, Vλ3-22, Vλ3-21, Vλ3-19, Vλ3-16, Vλ2-14, Vλ3-12, Vλ2-11, Vλ3-10, Vλ3-9, Vλ2-8, Vλ4-3, Vλ3-1, or any combination thereof, comprising human non-coding DNA naturally occurring adjacent to the endogenous human lambda light chain locus of human Vλ4-69, Vλ8-61, Vλ4-60, Vλ6-57, Vλ10-54, Vλ5-52, Vλ1-51, Vλ9-49, Vλ1-47, Vλ7-46, Vλ5-45, Vλ1-44, Vλ7-43, Vλ1 -40, Vλ5-39, Vλ5-37, Vλ1-36, Vλ3-27, Vλ3-25, Vλ2-23, Vλ3-22, Vλ3-21, Vλ3-19, Vλ3-16, Vλ2-14, Vλ3-12, Vλ2-11, Vλ3-10, Vλ3-9, Vλ2-8, Vλ4-3, or Vλ3-1, and an insertion of human Jλ1, Jλ2, Jλ3, Jλ6, Jλ7, or any combination thereof, comprising human non-coding DNA (in whole or in part) that naturally occurs in human Jκ1, Jκ2, Jκ3, Jκ4, or Jκ5 adjacent to the endogenous human κ light chain locus. In some embodiments of the provided non-human animals, non-human cells, or non-human tissues, the immunoglobulin κ light chain locus as described herein further comprises a human immunoglobulin κ light chain sequence that is located between one or more human Vλ gene segments, one or more human Jλ gene segments, one or more human Vλ gene segments, and one or more human Jλ gene segments, and combinations thereof. In some embodiments, the human immunoglobulin κ light chain sequence as described herein is or comprises a genomic sequence that naturally occurs between the human Vκ4-1 gene segment and the human Jκ1 gene segment of the immunoglobulin κ light chain locus. In some embodiments of the provided non-human animals, non-human cells, or non-human tissues, the germline genome of the non-human animal, non-human cell, or non-human tissue further comprises an endogenous immunoglobulin heavy chain locus comprising an insertion of one or more human V H Gene fragments, one or more human D H gene fragments, and one or more human J H Gene fragments, including human V H 、D H and J H Gene segments are non-human immunoglobulin heavy chain constant regions operably linked to endogenous immunoglobulin heavy chain loci (see, e.g., U.S. Patent Nos. 8,502,018, 8,642,835, 8,697,940, and 8,791,323, each of which is incorporated herein by reference in its entirety). In some embodiments, one or more human V H Gene fragments, one or more human D H gene fragments, and one or more human J H The gene segment replaces (in place of) or substitutes, in whole or in part, a non-human V H 、D H and J H Gene fragments (e.g., human V H 、D H With J H The coding sequence of the gene fragment is positioned to replace or substitute the non-human V H 、D H With J H In some embodiments, the insertion comprises human non-coding DNA that naturally occurs between human V H 、D H and J H In some embodiments, a non-human immunoglobulin heavy chain constant region is or comprises an endogenous non-human immunoglobulin heavy chain constant region. In many embodiments, the non-human immunoglobulin heavy chain constant region (e.g., endogenous) comprises one or more non-human immunoglobulin heavy chain constant region genes or gene fragments (e.g., IgM, IgD, IgG, IgE, IgA, etc.). In certain embodiments, the immunoglobulin heavy chain locus described herein comprises an insertion of a human V H γενε παράτηV H 3-74、V H 3-73、V H 3-72、V H 2-70、V H 1-69、V H 3-66、V H 3-64、V H 4-61、V H 4-59、V H 1-58、V H 3-53、V H 5-51、 V H 3-49、V H 3-48、V H 1-46、V H 1-45、V H 3-43、V H 4-39、V H 4-34、V H 3-33、V H 4-31、V H 3-30、V H 4-28、V H 2-26、V H 1-24、V H 3-23、V H 3-21、V H 3-20、V H 1-18、V H3-15, V H 3-13, V H 3-11, V H 3-9, V H 1-8, V H 3-7, V H 2-5, V H 7-4-1, V H 4-4, V H 1-3, V H 1-2, V H 6-1, or any combination thereof, human D H Gene fragment D H 1-1, D H 2-2, D H 3-3, D H 4-4, D H 5-5, D H 6-6, D H 1-7, D H 2-8, D H 3-9, D H 3-10, D H 5-12, D H 6-13, D H 2-15, D H 3-16, D H 4-17, D H 6-19, D H 1-20, D H 2-21, D H 3-22, D H 6-25, D H 1-26, D H 7-27, or any combination thereof, and human J H Gene fragment J H 1. J H 2. J H 3. J H 4. J H 5. J H 6, or any combination thereof. In certain embodiments, the insertion comprises human noncoding DNA that naturally occurs in a human V adjacent to the endogenous heavy chain locus. H 3-74, V H 3-73, V H 3-72, V H 2-70, V H 1-69, V H 3-66, V H 3-64, V H 4-61, V H 4-59, V H 1-58, V H 3-53, V H 5-51, V H 3-49, V H 3-48, V H 1-46, V H 1-45, V H 3-43, V H 4-39, V H 4-34, V H 3-33, V H 4-31, V H 3-30, V H 4-28, V H 2-26, V H 1-24, V H 3-23, V H 3-21, V H 3-20, V H 1-18, V H 3-15, V H 3-13, V H 3-11, V H 3-9, V H 1-8, V H 3-7, V H 2-5, V H 7-4-1, V H 4-4, V H 1-3, V H 1-2, or V H 6-1. Human non-coding DNA, which occurs naturally in close proximity to human D H 1-1, D H 2-2, D H 3-3, D H 4-4, D H 5-5, D H 6-6, D H 1-7, D H 2-8, D H 3-9, D H 3-10, D H 5-12, D H 6-13, D H 2-15, D H 3-16, D H 4-17, D H 6-19, D H 1-20, D H 2-21, D H 3-22, D H 6-25, D H 1-26, or D H 7-27, and human noncoding DNA that occurs naturally in the human J adjacent to the endogenous heavy chain locus. H 1. J H 2. J H 3. J H 4. J H 5, or J H . In some embodiments, the non-human animals described herein include an Adam6 gene in their genome (e.g., their germline genome) that encodes an ADAM6 polypeptide, its functional ortholog, functional homolog, or functional fragment (see, e.g., U.S. Patent Nos. 8,642,835 and 8,697,940, each of which is incorporated herein by reference in its entirety). In some embodiments, the ADAM6 polypeptide, its functional ortholog, functional homolog, or functional fragment is expressed by the Adam6 gene. In some embodiments, the Adam6 gene is not derived from a non-human animal comprising an Adam6 gene (e.g., a mouse comprising a rat Adam6 gene or a mouse Adam6 gene obtained from another mouse strain). In some embodiments, the non-human animals described herein include an ectopic Adam6 gene. As used herein, an "ectopic" Adam6 gene refers to an Adam6 gene that is different from the Adam6 gene that occurs in a wild-type non-human animal. For example, the Adam6 gene may be located on a different chromosome, at a different locus, or near a different sequence. An exemplary ectopic Adam6 gene is a mouse Adam6 gene located within a human immunoglobulin sequence (e.g., a human heavy chain variable region gene segment). In some embodiments, the non-human animals described herein include an inserted or integrated Adam6 gene. In some embodiments, the non-human animals described herein comprise one or more nucleotide sequences encoding one or more non-human Adam6 polypeptides, functional orthologs, functional homologs, or functional fragments thereof, inserted into their genome (e.g., their germline genome). In some embodiments, the non-human animals described herein include one or more nucleotide sequences encoding one or more non-human ADAM6 polypeptides, functional homologues, functional homologues or functional fragments thereof in their genome (e.g., their germline genome). In some embodiments, the non-human animals described herein include a mouse Adam6a gene and / or a mouse Adam6b gene in their genome (including their germline genome). In some embodiments, the non-human animals described herein include one or more nucleotide sequences of mouse ADAM6a, its functional homologues, functional homologues or functional fragments, and / or mouse ADAM6b, its functional homologues, functional homologues or functional fragments. In some embodiments, one or more nucleotide sequences encoding one or more non-human ADAM6 polypeptides, functional orthologs, functional homologs, or functional fragments thereof are inserted and / or located on the same chromosome as the endogenous immunoglobulin heavy chain locus. In some embodiments, one or more nucleotide sequences encoding one or more non-human ADAM6 polypeptides, functional orthologs, functional homologs, or functional fragments thereof are inserted and / or located in a position such that the one or more nucleotide sequences encoding one or more non-human ADAM6 polypeptides, functional orthologs, functional homologs, or functional fragments thereof are adjacent to a human immunoglobulin heavy chain variable region gene segment. In some embodiments, one or more nucleotide sequences encoding one or more non-human ADAM6 polypeptides, functional orthologs, functional homologs, or functional fragments thereof are inserted and / or located in a position such that the one or more nucleotide sequences encoding one or more non-human ADAM6 polypeptides, functional orthologs, functional homologs, or functional fragments thereof are adjacent to a human immunoglobulin heavy chain variable region gene segment. In some embodiments, one or more nucleotide sequences encoding one or more non-human ADAM6 polypeptides, functional orthologs, functional homologs, or functional fragments thereof are inserted and / or located in a position such that the one or more nucleotide sequences encoding one or more non-human ADAM6 polypeptides, functional orthologs, functional homologs, or functional fragments thereof are between human immunoglobulin heavy chain variable region gene segments. In some embodiments, one or more nucleotide sequences encoding one or more non-human ADAM6 polypeptides, functional orthologs, functional homologs, or functional fragments thereof are inserted and / or located between a first and a second human V H In some embodiments, the first human V H The gene segment is human V H 1-2, and the second human V H The gene segment is human V H 6-1. In some embodiments, one or more nucleotide sequences encoding one or more non-human ADAM6 polypeptides, their functional orthologs, functional homologs, or functional fragments are inserted into and / or located at the human Adam6 pseudogene. In some embodiments, one or more nucleotide sequences encoding one or more non-human ADAM6 polypeptides, their functional orthologs, functional homologs, or functional fragments are inserted into the human V H Gene fragments and human D H between gene fragments. In some embodiments, the non-human animals described herein include an Adam6 gene that can restore or enhance ADAM6 activity. In some embodiments, the Adam6 gene can restore ADAM6 activity to the level of a comparable non-human animal comprising a functional, endogenous Adam6 gene. In some embodiments, the Adam6 gene can enhance ADAM6 activity to at least 2 times, at least 3 times, at least 4 times, at least 5 times, at least 6 times, at least 7 times, at least 8 times, at least 9 times, or at least 10 times the ADAM6 activity of a comparable non-human animal that does not comprise the functional Adam6 gene. In some embodiments, the non-human animals described herein include an Adam6 gene that restores or enhances fertility in male non-human animals. In some embodiments, the Adam6 gene can restore fertility in male non-human animals to the level of a comparable non-human animal that includes a functional, endogenous Adam6 gene. In some embodiments, the Adam6 gene can restore fertility in male non-human animals such that the number of pups produced by mating with the male non-human animal is at least 70%, at least 80%, at least 90%, or at least 95% of the number of pups produced by mating with a comparable male non-human animal that does not include the functional Adam6 gene. In some embodiments, the Adam6 gene can enhance fertility in male non-human animals such that the number of pups produced by mating with the male non-human animal is at least 2 times, at least 3 times, at least 4 times, at least 5 times, at least 6 times, at least 7 times, at least 8 times, at least 9 times, or at least 10 times the number of pups produced by mating with a comparable male non-human animal that does not include the functional Adam6 gene. In some embodiments, the non-human immunoglobulin heavy chain locus as described herein lacks at least one endogenous non-human Adam6 gene. In some embodiments, the lack of at least one endogenous non-human Adam6 gene reduces ADAM6 activity and / or fertility in male mice lacking the endogenous non-human Adam6 gene. In some embodiments, the non-human immunoglobulin heavy chain locus as described herein comprises disruption of at least one endogenous non-human Adam6 gene. In some embodiments, disruption of at least one endogenous non-human Adam6 gene reduces ADAM6 activity and / or fertility in male mice lacking the endogenous non-human Adam6 gene. In some embodiments of the non-human animal, non-human cell, or non-human tissue, the endogenous immunoglobulin heavy chain locus of the non-human animal, non-human cell, or non-human tissue is homozygous or heterozygous, as described herein. In some embodiments of the non-human animal, non-human cell, or non-human tissue, the endogenous immunoglobulin kappa light chain locus of the non-human animal, non-human cell, or non-human tissue is homozygous or heterozygous, as described herein. In some embodiments of the non-human animals, non-human cells, or non-human tissues provided, the endogenous immunoglobulin lambda light chain locus is completely or partially deleted. In some embodiments of the non-human animals, non-human cells, or non-human tissues provided, the endogenous immunoglobulin lambda light chain locus is functionally silenced or non-functional (e.g., gene targeted). In some embodiments of the non-human animals, non-human cells, or non-human tissues provided, the functionally silenced or non-functional endogenous immunoglobulin lambda light chain locus of the non-human animals, non-human cells, or non-human tissues provided is homozygous or heterozygous, as described herein. In some embodiments, the non-human animal, non-human cell, or non-human tissue described herein does not detectably express endogenous immunoglobulin lambda light chains, endogenous immunoglobulin kappa light chains, or both endogenous immunoglobulin lambda light chains and endogenous immunoglobulin kappa light chains. In some embodiments, the non-human animal, non-human cell, or non-human tissue described herein has a genome further comprising a nucleic acid sequence encoding an exogenous terminal deoxynucleotidyl transferase (TdT) operably linked to a transcriptional control unit. In some embodiments, the transcriptional control unit comprises a RAG1 transcriptional control unit, a RAG2 transcriptional control unit, an immunoglobulin heavy chain transcriptional control unit, an immunoglobulin kappa light chain transcriptional control unit, an immunoglobulin lambda light chain transcriptional control unit, or any combination thereof. In some embodiments, the nucleic acid sequence encoding the exogenous TdT is located at the immunoglobulin kappa light chain locus, the immunoglobulin lambda light chain locus, the immunoglobulin heavy chain locus, the RAG1 locus, or the RAG2 locus. In some embodiments, the TdT is human TdT. In some embodiments, the TdT is a short isoform of TdT (TdTS). In some embodiments, the human Igλ light chain sequence comprises genetic material from (e.g., isolated or obtained from) or the same as a human Igλ light chain locus, wherein the human Igλ light chain sequence encodes an Ig light chain comprising a coding portion of genetic material from the human Igλ light chain locus. In some embodiments, the human Igλ light chain sequence as described herein comprises at least one human Vλ gene segment and at least one human Jλ gene segment, and one or more sequences (e.g., a recombination signal sequence) necessary to promote rearrangement of the at least one human Vλ gene segment with the at least one human Jλ gene segment to form a functionally rearranged human Vλ-Jλ sequence encoding a human Vλ domain. In many embodiments, the human Igλ light chain sequence comprises a plurality of human Vλ and Jλ gene segments, and one or more sequences necessary to promote rearrangement of the human Vλ gene segment with the Jλ gene segment. In many embodiments, the human Igλ light chain sequence comprises the coding sequence (e.g., exons) of at least one or more human Vλ gene segments and the coding sequence (e.g., exons) of at least one or more human Jλ gene segments. In some embodiments, the human Igλ light chain sequence described herein is a genomic sequence of a human Igλ light chain locus (e.g., isolated and / or cloned from a bacterial artificial chromosome) and comprises a plurality of Vλ gene segments in a human germline construct. In some embodiments, the human Igλ light chain sequence comprises human Vλ and Jλ sequences (i.e., gene segments) in a germline construct (i.e., a plurality of human Vλ gene segments isolated by intervening DNA, the DNA comprising sequences necessary for and promoting recombination, and a plurality of Jλ gene segments isolated by intervening DNA, the DNA comprising sequences necessary for and promoting recombination). In some embodiments, the human Igλ light chain sequences described herein are engineered sequences and comprise multiple human Jλ gene segments in a configuration different from that of the human Igλ light chain locus found in human cells. In some embodiments, the human Igλ light chain sequences described herein are engineered sequences and comprise multiple human Vλ and Jλ gene segments in a configuration similar to or analogous to the Igκ light chain locus found in wild-type murine or human cells. In some embodiments, the human Igλ light chain sequences comprise an engineered human Jλ sequence (i.e., The coding sequence of a human Jλ gene segment prepared by de novo DNA synthesis includes sequences necessary for and promoting recombination with one or more human Vλ gene segments. In some embodiments, the human Igλ light chain sequence comprises Igκ and Igλ sequences that naturally occur in the Igκ and Igλ genomic sequences, respectively. In certain embodiments, the human Igλ light chain sequence comprises an Igκ sequence, particularly a Jκ region (i.e., a sequence comprising one of coding and non-coding sequences that occurs in a region containing multiple Jκ gene segments), that naturally occurs in the Igκ light chain locus, except that the Igκ sequence contains the coding sequence of a Jλ gene segment and a Jλ12RSS, located in the corresponding coding sequence position of the Jκ gene segment and the Jκ23RSS. In certain embodiments, the human Igλ light chain sequence comprises multiple Jλ gene segments and a Jλ12RSS, located in the Jκ region sequence in the Jκ gene segment and Jκ23RSS position. In various embodiments, the intervening (or intergenic) DNA comprising sequences necessary for and promoting recombination comprises human Igκ and / or human Igλ genomic sequences. Furthermore, in some embodiments, the intervening (or intergenic) DNA comprising sequences necessary for and promoting recombination comprises murine Igκ and / or murine Igλ genomic sequences. In certain embodiments, the human Igλ light chain sequence is or comprises the sequence shown in the accompanying figures. In some embodiments, the human Igλ light chain sequence encodes, or is capable of encoding (e.g., after rearrangement of the human gene segments), a Vλ domain polypeptide, wherein the Vλ domain polypeptide is present in an immunoglobulin, particularly an immunoglobulin expressed by human B cells. Also provided are non-human animals, embryos, cells, and targeting constructs for producing non-human animals, embryos, and cells containing the human Igλ light chain sequence located at a corresponding non-human Igκ light chain sequence (e.g., an endogenous rodent Igκ light chain locus). In some embodiments, a human Igλ light chain sequence is inserted into the non-human animal's germline genome at a location corresponding to a non-human Igκ light chain sequence. In some embodiments, a human Igλ light chain sequence is inserted upstream of a non-human Igλ light chain sequence (e.g., a non-human Igλ light chain constant region gene sequence), wherein the non-human Igλ light chain sequence is located at a location corresponding to a non-human Igκ light chain sequence (e.g., a non-human Igκ light chain constant region gene sequence). In some embodiments, a human Igκ light chain sequence is inserted into the middle of the human Igλ light chain sequence (i.e., between the human Vλ and Jλ gene segments), such that the human Igκ light chain sequence is juxtaposed with the human Igλ light chain sequence. In some embodiments, all or substantially all of the variable regions at the non-human Igκ light chain locus are substituted or replaced with one or more human Igλ light chain sequences (as described herein), and the one or more human Igλ light chain sequences are operably linked to a non-human or human Igλ light chain constant region gene. In some embodiments, the non-human Igκ light chain constant region gene is deleted or replaced in a non-human animal comprising a human Igλ light chain sequence as described herein. In a non-limiting example, when a human Igλ light chain sequence is inserted into a non-human Igκ light chain locus, the insertion is performed in a manner that maintains the integrity of the non-human Igκ light chain enhancer region (or enhancer sequence) near the insertion point (e.g., the non-human Igκ intronic enhancer and / or the non-human Igκ 3' enhancer). Thus, such non-human animals have a wild-type Igκ light chain enhancer region (or enhancer sequence) operably linked to human and non-human Igλ light chain sequences (e.g., human Vλ and Jλ gene segments, and non-human Cλ region genes), or operably linked to human Igλ light chain sequences (e.g., human Vλ and Jλ gene segments, and human Cλ region genes). In some embodiments, the non-human Igκ light chain locus that is altered, replaced, disrupted, deleted, substituted, or engineered with one or more human Igλ light chain sequences described herein is a murine Igκ light chain locus. In some embodiments, one or more human Igλ light chain sequences as described herein are inserted into one of two copies (i.e., alleles) of the non-human Igκ light chain locus, resulting in a non-human animal that is heterozygous for a human Igκ light chain sequence. In some embodiments of the non-human animal, the non-human animal is heterozygous for a human Igκ light chain sequence, and the non-human animal comprises one or more human Igκ light chain sequences inserted into another copy (i.e., allele) of the non-human Igκ light chain locus. In some embodiments, a non-human animal is provided that is homozygous for an Igκ light chain locus and comprises one or more human Igλ light chain sequences as described herein. In some embodiments, the engineered non-human Igκ light chain locus as described herein comprises human Vλ and Jλ gene segments operably linked to a non-human or human Igλ light chain constant region gene, wherein the non-human or human Igλ light chain constant region gene is located at a non-human Igκ light chain constant region gene that occurs at a wild-type Igκ light chain locus in a non-human animal of the same species. In some embodiments, one or more endogenous non-human Igλ light chain sequences (or portions thereof) at an endogenous non-human Igλ light chain locus are not deleted. In some embodiments, one or more endogenous non-human Igλ light chain sequences (or portions thereof) at an endogenous non-human Igλ light chain locus are deleted. In some embodiments, one or more endogenous non-human Igλ light chain sequences (e.g., V, J, and / or C, or any combination thereof) at an endogenous non-human Igλ light chain locus are altered, replaced, disrupted, deleted, or substituted such that the non-human Igλ light chain locus is functionally silenced. In some embodiments, one or more endogenous non-human Igλ light chain sequences (e.g., V, J, and / or C, or any combination thereof) at an endogenous non-human Igλ light chain locus are altered, replaced, disrupted, deleted, or substituted such that the non-human Igλ light chain locus is functionally inactivated (i.e., unable to produce functional antibody light chains that can be expressed and / or detected in the antibody repertoire of a human animal). For example, guidance for inactivating an endogenous non-human Igλ light chain locus is provided in U.S. Patent No. 9,006,511 (see, for example, FIG. 2 ), which is incorporated herein by reference in its entirety. In some embodiments, a non-human animal contains an engineered Igκ light chain locus as described herein randomly integrated into its genome (e.g., as part of a randomly integrated human Igλ light chain sequence). Thus, such a non-human animal can be described as having a human Igλ light chain transgene comprising a plurality of human Vλ and Jλ gene segments operably linked to a non-human or human Igλ light chain constant region gene, and a non-human Igκ light chain enhancer region (or enhancer sequence), such that the human Vλ and Jλ gene segments are capable of rearranging and encoding Ig light chains for antibodies in the repertoire of the non-human animal, wherein the Ig light chain comprises a human Vλ domain and a non-human Cλ domain, or wherein the Ig light chain comprises human Vλ and Cλ domains. Detection of an engineered Igκ light chain locus or transgene as described herein can be performed using a variety of methods, including, for example, PCR, Western blots, Southern blots, restriction fragment length polymorphism (RFLP), or allele gain or loss assays. In some embodiments, the non-human animals described herein are heterozygous for the engineered Igκ light chain locus, as described herein. In some embodiments, the non-human animals described herein are hemizygous for the engineered Igκ light chain locus, as described herein. In some embodiments, the non-human animals described herein contain one or more copies of an engineered Igκ light chain locus or transgene, as described herein. In some embodiments, the non-human animals described herein contain an Igκ light chain locus as shown in the figures. The present invention recognizes that the non-human animals described herein utilize human heavy chain, lambda light chain, and kappa light chain variable region gene segments contained in their genomes in their antibody selection and production mechanisms (e.g., recombination and somatic hypermutation). Thus, in various embodiments, the human heavy chain, lambda light chain, and kappa light chain variable domains of human immunoglobulins produced by the non-human animals described herein are encoded by human heavy chain, lambda light chain, and kappa light chain variable region gene segments, respectively, included in their genomes or in somatic hypermutated variants thereof. In some embodiments, a non-human animal is provided whose genome comprises a modified immunoglobulin kappa light chain locus, wherein the non-human animal comprises a B cell comprising a human heavy chain variable region sequence, a human lambda light chain variable region sequence, and / or a somatically hypermutated human kappa light chain variable region sequence. In some embodiments, the human heavy chain variable region sequence, human lambda light chain, and / or human kappa light chain variable region sequence present in the mouse B cells of the present invention have 1, 2, 3, 4, 5, or more somatic hypermutations. Methods for identifying source gene segments in mature antibody sequences are known to those skilled in the art. For example, various tools can be used to assist in this analysis, for example, DNAPLOT, IMGT / V-QUEST, JOINSOLVER, SoDA, and Ab-origin. In particular, the present invention provides cells and tissues of non-human animals as described herein. In some embodiments, splenocytes (and / or other lymphoid tissue) of non-human animals as described herein are provided. In some embodiments, B cells of non-human animals as described herein are provided. In some embodiments, naive B cells of non-human animals as described herein are provided. In some embodiments, precursor B cells of non-human animals as described herein are provided. In some embodiments, immature B cells of non-human animals as described herein are provided. In some embodiments, mature naive B cells of non-human animals as described herein are provided. In some embodiments, activated B cells of non-human animals as described herein are provided. In some embodiments, memory B cells of non-human animals as described herein are provided. In some embodiments, B-lineage lymphocytes of non-human animals as described herein are provided. In some embodiments, plasma cells or plasma cells of non-human animals as described herein are provided. In some embodiments, stem cells of non-human animals as described herein are provided. In some embodiments, the stem cells are embryonic stem cells. In some embodiments, germ cells of non-human animals as described herein are provided. In some embodiments, the germ cells are oocytes. In some embodiments, the germ cells are sperm cells. In some embodiments, the sperm cells of non-human animals as described herein express one or more ADAM6 polypeptides, their functional homologs, functional homologs or functional fragments. In some embodiments, any cell or tissue of a non-human animal as described herein can be isolated. In some embodiments, isolated cells and / or isolated tissues of non-human animals as described herein are provided. In some embodiments, a fusion tumor is provided, wherein the fusion tumor is prepared from a non-human animal B cell as described herein. In some embodiments, the fusion tumor is prepared from a B cell of a non-human animal immunized with an antigen of interest. In some embodiments, the fusion tumor is prepared from a B cell of a non-human animal that expresses an antibody that binds (e.g., specifically binds) to an epitope on an antigen of interest. Any non-human animal as described herein can be immunized with one or more antigens of interest under conditions and for a time sufficient to allow the non-human animal to produce an immune response to the one or more antigens of interest. Methods for immunizing non-human animals are known to those skilled in the art. Exemplary, non-limiting methods for immunizing non-human animals can be found in US 2007 / 0280945A1, which is incorporated herein by reference in its entirety. In particular, the present disclosure provides immunized non-human animals as described herein, and cells and tissues isolated therefrom. In some embodiments, the non-human animals described herein produce a population of B cells in response to immunization with an antigen comprising one or more epitopes. In some embodiments, the non-human animals produce a population of B cells that express antibodies that bind (e.g., specifically bind) to one or more epitopes of the antigen of interest. In some embodiments, the antibodies expressed by the population of B cells produced in response to the antigen include a heavy chain having a human heavy chain variable domain encoded by a human heavy chain variable region sequence, and / or a lambda light chain having a human lambda light chain variable domain encoded by a human lambda light chain variable region sequence as described herein. In some embodiments, the antibodies expressed by a population of B cells produced in response to an antigen comprise (i) a heavy chain having a human heavy chain variable domain encoded by a human heavy chain variable region sequence, (ii) a lambda light chain having a human lambda light chain variable domain encoded by a human lambda light chain variable region sequence as described herein, (iii) a kappa light chain having a human kappa light chain variable domain encoded by a human kappa light chain variable region sequence as described herein, or (iv) any combination thereof. In some embodiments, the non-human animal produces a population of B cells that express antibodies that bind to one or more epitopes of an antigen of interest, wherein the antibodies expressed by the population of B cells produced in response to the antigen include: (i) a heavy chain having a human heavy chain variable domain encoded by a human heavy chain variable region sequence, (ii) a lambda light chain having a lambda light chain variable domain encoded by a human lambda light chain variable region sequence as described herein, (iii) a kappa light chain having a human kappa light chain variable domain encoded by a human kappa light chain variable region sequence as described herein, or (iv) any combination thereof. In some embodiments, the human heavy chain variable region sequence, human lambda light chain variable region sequence, and / or human kappa light chain variable region sequence as described herein are somatically hypermutated. In some embodiments, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% of the B cells in a population of B cells generated in response to an antigen comprise a human heavy chain variable region sequence, a human lambda light chain variable region sequence, and / or a human kappa light chain variable region sequence that are somatically hypermutated. In some embodiments, the non-human animals provided herein (1) comprise, in their germline genome, an engineered endogenous immunoglobulin κ light chain locus comprising (a) one or more human Vλ gene segments, (b) one or more human Jλ gene segments, and (c) a Cλ gene, wherein the one or more human Vλ gene segments and the one or more human Jλ gene segments are operably linked to the Cλ gene, (2) lack a rodent Cκ gene at the engineered endogenous immunoglobulin κ locus, and (3) comprise an engineered endogenous immunoglobulin κ light chain locus comprising (a) one or more human Vκ gene segments, (b) one or more human Jκ gene segments, and (c) a Cκ gene, wherein the one or more human Vκ gene segments and the one or more human Jκ gene segments are operably linked to the Cκ gene. In some embodiments, the percentage of light chains that are lambda light chains in the splenocytes of such non-human animals (e.g., as detected or observed by flow cytometry (see, e.g., Example 3)) is at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, or at least 75%. In some embodiments, the percentage of light chains that are lambda light chains in the splenocytes of such non-human animals (e.g., as detected or observed by flow cytometry (see, e.g., Example 3)) is between 35-80%, between 35-75%, between 40-80%, between 40-75%, between 50-80%, between 50-75%, between 55-80%, between 55-75%, between 60-80%, or between 60-75%. In some embodiments, the percentage of light chains that are kappa light chains in the splenocytes of such non-human animals (e.g., as detected or observed by flow cytometry (see, e.g., Example 3)) is at most 65%, at most 60%, at most 55%, at most 50%, at most 45%, at most 40%, or at most 35%. In some embodiments, the percentage of light chains that are kappa light chains in the splenocytes of such non-human animals (e.g., as detected or observed by flow cytometry (see, e.g., Example 3)) is between 20-65%, between 25-65%, between 20-60%, between 25-60%, between 20-55%, between 25-55%, between 20-50%, between 25-50%, between 20-45%, between 25-45%, between 20-40%, or between 25-40%.In some embodiments, the ratio of kappa: lambda light chains in the splenocytes of such non-human animals (e.g., as detected or observed by flow cytometry (see, e.g., Example 3)) is between 0.5:1 to 3:1, 0.65:1 to 3:1, between 0.8:1 to 3:1, between 1:1 to 3:1, between 1.2:1 to 3:1, between 1:1 to 2.3:1, between 1.1:1 to 1.8:1, between 1.2:1 to 2.3:1, or between 1.2:1 to 1.8:1. Method of producing the provided non-human animal Provided are compositions and methods for making a non-human animal having a germline genome comprising an engineered Igκ light chain locus comprising one or more human Igλ light chain sequences (e.g., human Vλ and Jλ gene segments) positioned at a non-human Igκ light chain sequence comprising human Igλ light chain coding sequences comprising a specific diversity of human Vλ and Jλ segments (e.g., specific V and / or J alleles or variants), including compositions and methods for making a non-human animal that expresses antibodies comprising Igλ light chains comprising human variable regions and non-human or human constant regions assembled from an Igκ light chain locus comprising human Vλ and Jλ gene segments operably linked to a non-human or human Igλ light chain constant region gene, wherein the non-human or human Igλ light chain constant region gene is positioned at a non-human Igκ light chain constant region gene that is normally present in a wild-type non-human Igκ light chain locus. In some embodiments, compositions and methods are provided for producing non-human animals that express such antibodies under the control of an endogenous Igκ enhancer and / or endogenous Igκ regulatory sequences. In some embodiments, compositions and methods are provided for producing non-human animals that express such antibodies under the control of a heterologous Igκ enhancer and / or heterologous Igκ regulatory sequences. The methods described herein comprise inserting human Vλ and Jλ sequences encoding a human Vλ domain upstream of a non-human or human Igλ light chain constant region gene (e.g., a mouse or human Cλ region gene), wherein the non-human or human Igλ light chain constant region gene is positioned at a non-human Igκ light chain constant region gene that is normally present at a wild-type non-human Igκ light chain locus, to express antibodies characterized by the presence of a light chain comprising a human Vλ domain and a non-human Cλ domain (e.g., a rodent Cλ domain), or the presence of a light chain comprising a human Vλ and a non-human Cλ domain (e.g., one or more rodent Cλ domains), and expressed on the surface of B cells and in the serum of the non-human animal. In some embodiments, the method comprises inserting genetic material containing human Vλ and Jλ gene segments into an Igκ light chain locus (e.g., a wild-type, modified, or engineered Igκ light chain locus). In certain embodiments, the method comprises inserting genetic material containing human Jλ gene segments into an Igκ light chain locus of a modified or engineered strain. In some embodiments, genetic material containing human Igλ light chain sequences can be engineered or genomicized (e.g., cloned from a bacterial artificial chromosome). In some embodiments, genetic material containing human Igλ light chain sequences can be engineered from a public source and / or engineered from a bacterial artificial chromosome such that the genetic material contains human Vλ and Jλ segments in an orientation different from that found in the human Igλ light chain locus, but the genetic material still contains sequences that support rearrangement of the human Vλ and Jλ segments to encode a functional human Vλ domain of an Ig light chain. For example, using the guidance provided herein, genetic material corresponding to a plurality of human Vλ and Jλ gene segments can be designed to construct a human Igλ light chain sequence containing human Vλ and Jλ segments in an order and / or arrangement that differs from that found in the human Igλ light chain locus in human cells (e.g., an arrangement similar to or similar to that of a human or rodent Igκ light chain locus, e.g., a series of V gene segments followed by a series of J gene segments 3' by inserting intervening DNA). In this example, the genetic material of the human Vλ and Jλ gene segments will be identical to the corresponding segments in human cells, however, the order and arrangement may differ. When constructing an engineered Igκ light chain locus to generate a non-human animal as described herein, the necessary recombination signal sequences can be configured so that the human V and J gene segments can correctly rearrange and form functional human Vλ domains. A guide to the sequences necessary for germline configuration and proper recombination of human Vλ and Jλ gene segments can be found, e.g., in Molecular Biology of B Cells, London: Elsevier Academic Press, 2004, Honjo, T., Alt, FW, Neuberger, M., eds., Chapter 4 (pp. 37-59) and Chapter 5 (pp. 61-82); which is incorporated herein by reference in its entirety. In some embodiments, the method comprises multiple insertions in a single ES cell clone. In some embodiments, the method comprises sequential insertions in consecutive ES cell clones. In some embodiments, the method comprises a single insertion in a modified ES cell clone. In some embodiments, the method comprises inserting DNA upstream of a murine Cλ1 gene (or a human Cλ2 gene) such that the DNA insert is operably linked to the murine Cλ1 gene (or human Cλ2 gene), wherein the DNA insert comprises human Vλ gene segments Vλ4-69, Vλ8-61, Vλ4-60, Vλ6-57, Vλ10-54, Vλ5-52, Vλ1-51, Vλ9-49, Vλ1-47, Vλ7-46, Vλ5-45, Vλ1-44, Vλ7-43, Vλ1-40, Vλ5-39, Vλ5-37, Vλ1-36, Vλ3-27, Vλ3-25, Vλ2-23, Vλ3-22, Vλ3-21, Vλ3-19, Vλ3-16, Vλ2-14, Vλ3-12, Vλ2-11, Vλ3-10, Vλ3-9, Vλ2-8, Vλ4-3, Vλ3-1, or any combination thereof, and human Jλ gene segments Jλ1, Jλ2, Jλ3, Jλ6, Jλ7, or any combination thereof, and wherein the murine Cλ1 gene (or human Cλ2 gene) is located at the murine Cκ gene of the endogenous Igκ light chain locus. In some embodiments, the method comprises inserting DNA downstream of a human Vλ3-1 gene segment and upstream of a non-human Igκ intronic enhancer region (or enhancer sequence) of an engineered Igκ light chain locus, such that the DNA insert is operably linked to the mouse Cλ1 gene (or human Cλ2 gene), wherein the DNA insert comprises a human Igκ genomic sequence that naturally occurs between the human Vκ4-1 gene segment and the human Jκ1 gene segment of the human Igκ light chain locus, and one or more human Jλ gene segments (e.g., one, two, three, four, five, six, or seven), wherein the mouse Cλ1 gene (or human Cλ2 gene) is positioned at the position of a mouse Cκ gene of the endogenous non-human Igκ light chain locus. In certain embodiments, the method comprises inserting DNA between a human Vλ3-1 gene segment and a non-human Igκ intronic enhancer, wherein the DNA insertion comprises a human Vκ-Jκ sequence that naturally occurs between the human Vκ4-1 and Jκ1 gene segments and five human Jλ gene segments (e.g., Jλ1, Jλ2, Jλ3, Jλ6, and Jλ7) at the human Igκ light chain locus. In various embodiments, the DNA insertion comprising the human Jλ gene segment comprises human Jκ genomic DNA comprising the coding sequence of the human Jλ gene segment and the human Jλ12 RSS. Using the methods described herein, it is possible to insert additional human Vλ and Jλ segments to further supplement the diversity of the engineered Igλ light chain locus. For example, in some embodiments, the method may comprise inserting approximately 270 kb of DNA upstream of the murine Cλ1 gene (or human Cλ2 gene) of the engineered Igκ light chain locus, such that the DNA is operably linked to the mouse Cλ1 gene (or human Cλ2 gene), wherein the DNA comprises human Vλ gene segments Vλ10-54, Vλ6-57, Vλ4-60, Vλ8-61, and Vλ4-69. In such embodiments, the DNA is inserted upstream of the human Vλ5-52 gene segment, which is operably linked to the mouse Cλ1 gene (or human Cλ2 gene) of the engineered Igκ light chain locus, wherein the DNA comprises human Vλ gene segments Vλ10-54, Vλ6-57, Vλ4-60, Vλ8-61, and Vλ4-69. In certain embodiments, the DNA comprises a human VpreB gene. The additional human Vλ gene segments described above can be cloned directly from commercially available BAC clones and arranged into smaller DNA fragments using recombinant techniques described herein or known in the art. In addition, the additional human Vλ gene segments described above can be synthesized as modified DNA fragments and added to the modified Igκ light chain locus described above using molecular biology techniques known in the art. Similarly, additional human Jλ gene segments can be obtained from commercially available BAC clones or synthesized directly from published sequences. Illustrative illustrations of modified Igκ light chain loci for non-human animals as described herein are shown in Figures 2B or 4B. Where appropriate, human Igλ light chain sequences encoding human Vλ domains (i.e., sequences comprising human Vλ and Jλ gene segments) can be individually modified to include codons optimized for expression in non-human animals (e.g., see U.S. Patent Nos. 5,670,356 and 5,874,304). A codon-optimized sequence is a modified sequence that preferably encodes the same polypeptide encoded by the non-codon-optimized parent polynucleotide (or a biologically active fragment of the full-length polypeptide having substantially the same activity as the full-length polypeptide). In some embodiments, human Igλ light chain sequences encoding human Vλ domains can each include altered sequences to optimize codon usage for a specific cell type (e.g., rodent cells). For example, the codons of each nucleotide sequence to be inserted into the genome of a non-human animal (e.g., a rodent) can be optimized for expression in the cells of the non-human animal. Such sequences can be described as codon-optimized sequences. Insertion of a nucleotide sequence encoding a human Vλ domain uses minimal modification of the non-human animal germline genome as described herein and results in the expression of antibodies comprising light chains having human Vλ domains, wherein the human Vλ domains are expressed from endogenous engineered Igκ light chain loci. Methods for generating engineered non-human animals, including knockouts and insertions, are known in the art (see, e.g., Gene Targeting: A Practical Approach, Joyner, ed., Oxford University Press, Inc., 2000; which is incorporated herein by reference in its entirety). For example, the generation of genetically modified rodents can optionally involve disrupting the locus of one or more endogenous rodent genes (or gene fragments) and introducing one or more heterologous genes (or gene fragments or nucleotide sequences) into the rodent genome, in some embodiments, at the same location as the endogenous rodent gene (or gene fragment). In some embodiments, a nucleotide sequence encoding a human Vλ domain is introduced upstream of a murine or human Igλ light chain constant region gene of a randomly inserted engineered light chain transgene into the genome of a rodent germline cell line. In some embodiments, a nucleotide sequence encoding a human Vλ domain is introduced upstream of a murine or human Igλ light chain constant region gene at an endogenous Igκ light chain locus in the genome of a rodent germline cell line; in certain embodiments, the endogenous Igκ light chain locus is altered, modified, or engineered to contain a human Igλ gene segment (e.g., human V and J) operably linked to a mouse Cλ1 gene or to a human Cλ2 gene. Schematic diagrams (not to scale) of exemplary methods for constructing engineered Igκ light chain loci as described herein are provided in Figures 1A, 1B, 2A, 2B, 3, 4A, and 4B. In particular, Figures 1A and 1B set forth exemplary strategies for constructing engineered Igκ light chain loci characterized by the insertion of nucleotide sequences containing multiple human Vλ and Jλ gene segments. As shown in Figures 1A and 1B, a DNA fragment containing the human Vκ-Jκ intergenic region (see U.S. Patent Nos. 9,006,511, 9,012,717, 9,029,628, 9,035,128, 9,066,502, 9,150,662, and 9,163,092) and an engineered fragment containing a set of human Jλ gene segments (e.g., human Jλ1, Jλ2, Jλ3, Jλ6, and Jλ7) are operably linked to a rodent Igκ intronic enhancer region (or enhancer sequence) through a series of steps using various molecular biology techniques described in Example 1. This engineered fragment is also engineered to contain a rodent Igλ light chain constant region operably linked to the human Jλ gene segment. Selection cassettes (e.g., neomycin and hygromycin) are included in the targeting vector to allow selection of positive replicators in bacteria and mammalian cells (e.g., embryonic stem cells). The lox2372 site-specific recombination site (lox) is located between the human Vκ-Jκ region and the human Jλ gene segment group, and the hygromycin selection cassette is flanked by loxP site-specific recombination site, and located at the 3' end of the rodent Igλ light chain constant region (mCλ1) gene. This DNA fragment was then combined with a DNA fragment containing the rodent Igκ light chain 3' enhancer to produce the final targeting vector (Figure 1B). The resulting targeting vector (Construct G) was linearized and electroporated into rodent embryonic stem (ES) cells to create rodents whose germline genomes contained a modified Igκ light chain locus. As described in the Examples section below, rodent ES cells used for targeting vector electroporation contained a modified Igκ light chain locus, as previously described in U.S. Patent Nos. 9,006,511, 9,012,717, 9,029,628, 9,035,128, 9,066,502, 9,150,662, and 9,163,092; which are incorporated herein by reference in their entirety. As depicted in Figure 3, homologous recombination with a targeting vector can produce an engineered Igκ light chain locus characterized by multiple human Vλ and Jλ gene segments operatively linked to the murine Cλ1 gene, wherein the mouse Cλ1 gene is located at the position of the mouse Cκ gene, which naturally occurs in the wild-type Igκ light chain locus. The human Jλ gene segments are uniquely engineered to contain sequences that do not naturally occur in the human Jκ region of the genome, but instead possess human Jλ coding sequences and associated 12RSSs, located at the positions of human Jκ coding sequences and associated 23RSSs. Positive rodent ES cell replicating lines are confirmed using screening methods described herein and / or known in the art. Any remaining screening cassettes can be deleted as needed by recombinase-mediated deletion (see Example 2). Furthermore, a human Cλ gene can be used in the targeting vector instead of a mouse Cλ gene. For example only, FIG3 illustrates a targeting vector constructed in a similar manner to that described above, except that the sequence encoding the human Cλ2 gene is engineered into the targeting vector and operably linked to five human Jλ gene segments. Using this approach offers additional benefits in developing human antibody therapeutics because the DNA encoding the light chain variable and constant regions can be isolated together, thereby eliminating any subsequent cloning steps required to link the human light chain constant region to produce a fully human antibody. The targeting vector used to construct the modified Igκ light chain locus as described herein can be added to the germline genome of a non-human cell (e.g., a rodent embryonic stem cell). In some embodiments, the targeting vector as described herein is added to the wild-type Igκ light chain locus of the germline genome of a non-human cell, wherein the cell further comprises a human V H 、D H and J HGenomic DNA (e.g., containing multiple human V H 、D H and J H gene segments) operably linked to one or more immunoglobulin heavy chain constant region genes (e.g., see U.S. Patent Nos. 8,502,018, 8,642,835, 8,697,940, and 8,791,323, each of which is incorporated herein by reference in its entirety). In some embodiments, a targeting vector as described herein is added to a modified or engineered immunoglobulin kappa light chain locus in the germline genome of a non-human cell, the non-human cell further comprising a human V H 、D H and J H Genomic DNA (e.g., containing multiple human V H 、D H and J H gene segments) that are operably linked to one or more immunoglobulin heavy chain constant region genes (see, e.g., U.S. Patent Nos. 8,502,018, 8,642,835, 8,697,940, 8,791,323, 9,006,511, 9,012,717, 9,029,628, 9,035,128, 9,066,502, 9,150,662, and 9,163,092, each of which is herein incorporated by reference in its entirety). A targeting vector is introduced into rodent (e.g., mouse) embryonic stem cells via electroporation, such that the sequence contained in the targeting vector confers the ability of the non-human cell or non-human animal (e.g., mouse) to express an antibody having a light chain comprising a human Vλ domain and a non-human or human Cλ domain, wherein the light chain is expressed from an endogenous engineered immunoglobulin κ light chain locus. As described herein, a genetically modified rodent is generated wherein an engineered immunoglobulin κ light chain locus (e.g., an endogenous immunoglobulin κ light chain locus comprising a human Igλ light chain sequence (i.e., multiple human Vλ and Jλ gene segments) operably linked to a rodent or human Cλ gene located at the endogenous rodent Cκ gene) is generated in the genome of the rodent's germline. Antibodies are expressed on the surface of rodent B cells and in the serum of the rodent, wherein the antibody is characterized in that its light chain comprises a human Vλ domain and a non-human or human Cλ domain. When the endogenous immunoglobulin kappa light chain locus in the rodent germline genome is not targeted by the targeting vector, the engineered immunoglobulin kappa light chain transgene is preferably inserted at a location other than the endogenous rodent immunoglobulin kappa light chain locus (e.g., a random insertion of the transgene). As described above, the generation of engineered immunoglobulin kappa light chain loci in non-human animals provides engineered rodent strains that can produce antibodies comprising immunoglobulin lambda light chains expressed from an immunoglobulin kappa light chain locus having a human Vλ domain and a non-human or human Cλ domain. H 、D H and J H The gene segments, operatively linked to immunoglobulin heavy chain constant region genes, create engineered rodent strains that produce antibodies and antibody components for the development of human antibody-based therapeutics. This creates a single engineered rodent strain with the potential to provide another in vivo system for exploring human Vλ domains to develop novel antibody-based drugs for the treatment of human diseases. In some embodiments, a method for producing a non-human animal whose germline genome comprises a modified endogenous immunoglobulin kappa light chain locus is provided, the method comprising (a) introducing a DNA fragment into a non-human embryonic stem cell, the DNA fragment comprising a nucleotide sequence comprising (i) one or more human Vλ gene segments, (ii) one or more human Jλ gene segments, and (iii) a Cλ gene (e.g., non-human or human), wherein (i)-(iii) are operably linked, and wherein the nucleotide sequence further comprises an immunoglobulin kappa light chain sequence between (i) and (ii), (b) obtaining the non-human embryonic stem cell produced in (a); and (c) producing a rodent using the rodent embryonic stem cell of (b). In some embodiments, a method for producing a non-human animal whose germline genome comprises an altered endogenous immunoglobulin κ light chain gene is provided, the method comprising (a) introducing a DNA fragment into a non-human embryonic stem cell, the DNA fragment comprising a nucleotide sequence comprising one or more human Jλ gene segments, one or more non-human immunoglobulin κ light chain enhancers, and a non-human or human Cλ gene, wherein the human Jλ gene segment is operably linked to the one or more non-human immunoglobulin κ light chain enhancers and the non-human or human Cλ gene, (b) obtaining the non-human embryonic stem cell produced in (a); and (c) producing a rodent using the rodent embryonic stem cell of (b). In some embodiments, a method is provided for producing a non-human animal having a germline genome comprising a modification of an endogenous immunoglobulin κ light chain locus, wherein the modified endogenous immunoglobulin κ light chain locus comprises the insertion of one or more human Vλ gene segments, one or more human Jλ gene segments, and a non-human or human Cλ gene, wherein the human Vλ and Jλ gene segments are operably linked to the non-human or human Cλ gene, and the non-human C or human Cλ gene is inserted at a position located at the endogenous immunoglobulin κ light chain locus. The method comprises modifying the germline genome of a non-human animal to comprise a modified endogenous immunoglobulin κ light chain locus by inserting one or more human Vλ gene segments, one or more human Jλ gene segments, and a non-human or human Cλ gene, wherein the human Vλ and Jλ gene segments are operably linked to the non-human or human Cλ gene, and wherein the non-human or human Cλ gene is inserted at a non-human CK gene located at the endogenous immunoglobulin κ locus. In some embodiments of the non-human animal production method, the one or more human Vλ gene segments include at least 24, at least 34, at least 52, at least 61, or at least 70 human Vλ gene segments. In some embodiments of the non-human animal production method, the one or more human Vλ gene segments include 39 human Vλ gene segments. In certain embodiments of the non-human animal manufacturing method, the one or more human Vλ gene segments include human Vλ4-69, Vλ8-61, Vλ4-60, Vλ6-57, Vλ10-54, Vλ5-52, Vλ1-51, Vλ9-49, Vλ1-47, Vλ7-46, Vλ5-45, Vλ1-44, Vλ7-43, Vλ1-40, Vλ5-39, Vλ5-37, Vλ1-36, Vλ3-27, Vλ3-25, Vλ2-23, Vλ3-22, Vλ3-21, Vλ3-19, Vλ3-16, Vλ2-14, Vλ3-12, Vλ2-11, Vλ3-10, Vλ3-9, Vλ2-8, Vλ4-3, Vλ3-1, or any combination thereof. In certain embodiments, the one or more human νλ gene segments comprise human non-coding DNA that naturally occurs adjacent to the relevant human νλ gene segment in the endogenous human λ light chain locus. In some embodiments of the non-human animal production method, the one or more human Jλ gene segments include at least 1, at least 2, at least 3, at least 4, or at least 5 human Jλ gene segments. In some embodiments of the non-human animal production method, the one or more human Jλ gene segments include 5 human Jλ gene segments. In some embodiments of the non-human animal production method, the one or more human Jλ gene segments include human Jλ1, Jλ2, Jλ3, Jλ6, Jλ7, or any combination thereof. In certain embodiments, the one or more human Jλ gene segments include human non-coding DNA (all or part) that naturally occurs adjacent to the relevant human Jλ gene segment in the endogenous human λ light chain locus. In some embodiments, the one or more human Jλ gene segments include human non-coding DNA that naturally occurs adjacent to human Jκ1-Jκ5 in the endogenous human κ light chain locus. In some embodiments of the methods for producing non-human animals, the DNA segments include intergenic DNA containing non-coding immunoglobulin DNA (e.g., DNA naturally occurring between coding sequences adjacent to two V gene segments, a V and J gene segment, or two J gene segments). In many embodiments, the non-coding immunoglobulin DNA is non-coding immunoglobulin light chain DNA (e.g., human or murine). In some embodiments, the non-coding immunoglobulin light chain DNA is immunoglobulin kappa light chain DNA, immunoglobulin lambda light chain DNA, or a combination thereof. In some embodiments of the non-human animal production method, the DNA fragment further comprises one or more selection markers. In some embodiments of the non-human animal production method, the DNA fragment further comprises one or more site-specific recombination sites. In some embodiments of the non-human animal production method, the DNA fragment further comprises one or more sets of site-specific recombination sites that are recombined with the same recombinase. In some embodiments of the non-human animal production method, the DNA fragment further comprises one or more sets of site-specific recombination sites that are recombined with different recombinases. In some embodiments of the non-human animal production methods, the DNA segment comprises a modified sequence comprising an immunoglobulin kappa light chain sequence and an immunoglobulin lambda light chain sequence, combined in a contiguous sequence. In some embodiments of the non-human animal production methods, the DNA segment comprises a modified sequence comprising an immunoglobulin kappa light chain sequence and an immunoglobulin lambda light chain sequence, combined in a single sequence with an intervening non-immunoglobulin sequence (e.g., a recombination signal sequence, a resistance gene, and combinations thereof). In some embodiments of the non-human animal production methods, the modified sequence comprises a portion of the Jκ region and a portion of the Jλ region. In some embodiments, the modified sequence comprises a portion of the human Jκ region and a portion of the human Jλ region. In certain embodiments, the portion of the human Jκ region comprises non-coding sequences of the human Jκ region that naturally occur in the human immunoglobulin kappa light chain locus in human cells. In certain embodiments, the portion of the human Jλ region comprises the coding sequence of one or more human Jλ gene segments and a recombination signal sequence (RSS). In some embodiments of the methods for producing non-human animals, the DNA segment comprises a modified sequence, which in some embodiments is characterized by the presence of a coding sequence and a recombination signal sequence (RSS) of one or more human Jλ gene segments, which are positioned to replace or displace (i.e., positioned within) the corresponding coding sequence and recombination signal sequence (RSS) on the human Jκ gene segment, such that the coding sequence and recombination signal sequence (RSS) of the one or more human Jλ gene segments are located within, adjacent to, continuous with, or juxtaposed to the non-coding sequence of the one or more human Jκ gene segments. In some embodiments of the methods for producing non-human animals, a DNA segment is introduced into a non-human embryonic stem cell whose germline genome comprises one or more engineered immunoglobulin loci (e.g., immunoglobulin heavy chains, immunoglobulin kappa light chains, immunoglobulin lambda light chains, and combinations thereof). In certain embodiments, the engineered immunoglobulin loci are endogenous engineered immunoglobulin loci. In some embodiments of the methods for producing a non-human animal, a DNA segment is introduced into a non-human embryonic stem cell whose germline genome comprises an endogenous immunoglobulin heavy chain locus comprising one or more human V H Gene fragments, one or more human D H gene fragments, and one or more human J H gene fragment, wherein the human V H 、D H and J H The gene segment is operably linked to a non-human immunoglobulin heavy chain constant region. In some embodiments of the methods for producing a non-human animal, a DNA segment is introduced into a non-human embryonic stem cell, the germline genome of which comprises an endogenous immunoglobulin κ light chain locus comprising an insertion of one or more human Vλ and one or more human Jλ gene segments, wherein the human Vλ and Jλ gene segments are operably linked to a non-human immunoglobulin κ light chain constant region gene. In some embodiments of the methods for producing a non-human animal, a DNA segment is introduced into a non-human embryonic stem cell, the germline genome of which comprises an endogenous immunoglobulin κ light chain locus comprising an insertion of one or more human Vλ and one or more human Jλ gene segments, and a human immunoglobulin κ light chain sequence is positioned, positioned, or located between the one or more human Vλ gene segments and the one or more human Jλ gene segments, wherein the human Vλ and Jλ gene segments are operably linked to a non-human immunoglobulin κ light chain constant region gene. In some embodiments of the methods for producing a non-human animal, modifying the germline genome of the non-human animal to include an engineered immunoglobulin kappa light chain locus is performed in a non-human embryonic stem cell, the germline genome of which includes an endogenous immunoglobulin heavy chain locus comprising an insertion of one or more human V H Gene fragments, one or more human D H gene fragments, and one or more human J H gene fragment, wherein the human V H 、D H and J H The gene segment is operably linked to a non-human immunoglobulin heavy chain constant region. In some embodiments of the methods for producing a non-human animal, modifying the germline genome of the non-human animal to contain a modified immunoglobulin κ light chain locus is performed in a non-human embryonic stem cell, the germline genome of which contains an endogenous immunoglobulin κ light chain locus comprising an insertion of one or more human Vλ and one or more human Jλ gene segments, wherein the human Vλ and Jλ gene segments are operably linked to a non-human immunoglobulin κ light chain constant region gene. In some embodiments of the methods for producing a non-human animal, modifying the germline genome of the non-human animal to comprise a modified immunoglobulin κ light chain locus is performed in non-human embryonic stem cells, the germline genome of which comprises an endogenous immunoglobulin κ heavy chain locus comprising an insertion of one or more human νλ gene segments, one or more human Jλ gene segments, and a human immunoglobulin κ light chain sequence positioned, positioned, or located between the one or more human νλ gene segments and the one or more human Jλ gene segments, wherein the human νλ and Jλ gene segments are operably linked to a non-human immunoglobulin κ light chain constant region gene. In some embodiments of the non-human animal manufacturing method, one or more human V H Gene fragments, one or more human D H gene fragments, and one or more human J H Gene segments, including naturally occurring genes adjacent to human V H Human non-coding DNA fragments that occur naturally adjacent to human D H gene segments, and naturally occurring human J H Human non-coding DNA gene fragments. In some embodiments, non-human animals prepared, produced, manufactured, obtained, or obtainable by the methods described herein are provided. In some embodiments, the non-human animal genome described herein further comprises one or more human immunoglobulin heavy chain variable regions, as described in U.S. Patent Nos. 8,502,018, 8,642,835, 8,697,940, and 8,791,323, each of which is incorporated herein by reference in its entirety. In addition, the modified immunoglobulin kappa light chain loci described herein can be transformed into embryonic stem cells of different modified strains, such as the VELOCIMMUNE® strain (see, e.g., U.S. Patent Nos. 8,502,018 and / or 8,642,835; incorporated herein by reference in their entirety). Homozygosity for the modified Ig kappa light chain loci as described herein can then be achieved through breeding. Alternatively, in the case of random insertion of a modified immunoglobulin kappa light chain transgene (as described above), rodent strains can be screened based on, for example, the expression of human Vλ domains from the transgenic strain. In some embodiments, the VELOCIMMUNE® mouse can be a VELOCIMMUNE® 1 (VI-1) mouse, which includes 18 human V H Gene segments, all human D H Gene fragments and all J H Gene segments. VI-1 mice may also include 16 human Vκ gene segments and all human Jκ gene segments. In some embodiments, the VELOCIMMUNE® mouse may be a VELOCIMMUNE® 2 (VI-2) mouse, which includes 39 human V H Gene fragments, all human D H Gene fragments and all J H Gene segments. VI-2 mice may also include 30 human Vκ gene segments and all human Jκ gene segments. In some embodiments, the VELOCIMMUNE® mouse may be a VELOCIMMUNE® 3 (VI-3) mouse, which includes 80 human Vκ gene segments and all human Jκ gene segments. H Gene segments, all human D H Gene fragments and all J H Gene segments. VI-3 mice can also include all 40 human Vκ gene segments and all human Jκ gene segments. Additionally and / or additionally, in some embodiments, the germline genome of a non-human animal as described herein further comprises a deletion, inactivation, functional silencing, or other non-functional endogenous immunoglobulin lambda light chain locus. Genetic modification to delete or generate a non-functional gene or locus can be achieved using the methods described herein and / or methods known in the art. A genetically modified founder non-human animal can be identified based on the presence of a modified Ig kappa light chain locus in its germline genome and / or the expression of antibodies having a human Vλ domain and a non-human or human Cλ domain in tissues or cells of the non-human animal. The genetically modified founder non-human animal can then be used to breed additional non-human animals carrying the modified immunoglobulin kappa light chain locus, thereby creating a population of non-human animals, each carrying one or more copies of the modified immunoglobulin kappa light chain locus. Furthermore, genetically modified non-human animals carrying a modified immunoglobulin kappa light chain locus as described herein can be further bred with other genetically modified non-human animals carrying other transgenes (e.g., human immunoglobulin genes) or modified immunoglobulin loci. Genetically modified non-human animals can also be generated that contain selected systems that allow for the regulation, targeting, induction, and / or cell type-specific expression of transgenes or incorporated sequences. For example, non-human animals as described herein can be engineered to contain one or more sequences encoding human Vλ domains of conditionally expressed antibodies (as reviewed in Rajewski, K. et al., 1996, J. Clin. Invest. 98(3):600-3, which is incorporated herein by reference in its entirety). Exemplary systems include the Cre / loxP recombinase system (see, e.g., Lakso, M. et al., 1992, Proc. Natl. Acad. Sci. USA 89: 6232-6, which is incorporated herein by reference in its entirety), and the FLP / Frt recombinase system of S. cerevisiae (O'Gorman, S. et al., 1991, Science 251: 1351-5, which is incorporated herein by reference in its entirety). Such animals can be constructed by "Double" genetically modified animals can be provided, for example, by mating two genetically modified animals, one of which contains a transgene comprising the modification selected for (e.g., a modified Ig kappa light chain locus, as described herein) and the other contains a transgene encoding a recombinase (e.g., Cre recombinase). Non-human animals as described herein can be prepared as described above, or using methods known in the art, to include additional human, humanized, or other modified genes, generally depending on the intended use of the non-human animal. Such human, humanized, or other modified genetic material can be introduced by further altering the genome of cells (e.g., embryonic stem cells) having the genetic modifications or alterations described above, or by breeding techniques and other genetically modified or modified strains known in the art, as desired. In some embodiments, a non-human animal as described herein is prepared to further comprise a human IgH and / or Ig kappa light chain gene or gene fragment (see, e.g., Murphy, AJ, et al. (2014) Proc. Natl. Acad. Sci. USA 111(14):5153-5158; U.S. Patent Nos. 8,502,018, 8,642,835, 8,697,940, and 8,791,323; U.S. Patent No. 8,791,323; and U.S. Patent Application Publication No. 2013 / 0096287 A1; each of which is herein incorporated by reference in its entirety). In some embodiments, non-human animals as described herein can be prepared by introducing targeting vectors as described herein into cells from modified or transformed strains. For example, targeting vectors as described herein can be introduced into VELOCIMMUNE® mice. VELOCIMMUNE® mice express antibodies with complete human variable regions and mouse constant regions. In another example, targeting vectors as described herein can be introduced into transformed mice, as described in U.S. Patent Nos. 9,006,511, 9,012,717, 9,029,628, 9,035,128, 9,066,502, 9,150,662, and 9,163,092, which are incorporated herein by reference in their entirety. In some embodiments, non-human animals as described herein are prepared to further comprise human immunoglobulin genes (variable region and / or constant region genes). In some embodiments, a non-human animal as described herein comprises an engineered Igκ light chain locus as described herein, and genetic material from a heterologous species (e.g., human), wherein the genetic material (in whole or in part) encodes one or more human heavy chain and / or Igκ light chain variable regions. For example, as described herein, a non-human animal comprising an engineered Igκ light chain locus as described herein can further comprise (e.g., via cross-breeding or a multigene targeting strategy) one or more modifications as described in Murphy, AJ et al., (2014) Proc. Natl. Acad. Sci. USA 111(14):5153-8; Macdonald, LE et al., 2014, Proc. Natl. Acad. Sci. USA 111(14):5147-52; US Patent Nos. 8,502,018, 8,642,835, 8,697,940, and 8,791,323; all of which are incorporated herein by reference in their entirety. In some embodiments, rodents comprising an engineered immunoglobulin kappa light chain locus as described herein are crossed with rodents comprising humanized immunoglobulin heavy chain and / or immunoglobulin kappa light chain variable region loci (see, e.g., U.S. Patent Nos. 8,502,018, 8,642,835, 8,697,940, and / or 8,791,323; herein incorporated by reference in their entireties). In some embodiments, rodents comprising an engineered immunoglobulin kappa light chain locus as described herein are crossed with rodents comprising a humanized immunoglobulin heavy chain locus (see, e.g., U.S. Pat. Nos. 8,502,018, 8,642,835, 8,697,940, and / or 8,791,323; herein incorporated by reference in their entireties), and an inactivated endogenous immunoglobulin lambda light chain locus (see, e.g., U.S. Pat. Nos. 9,006,511, 9,012,717, 9,029,628, 9,035,128, 9,066,502, 9,150,662, and 9,163,092, herein incorporated by reference in their entireties). While embodiments of constructing a modified immunoglobulin kappa light chain locus in mice (i.e., mice having a modified immunoglobulin kappa light chain locus characterized by the presence of multiple human Vλ and Jλ gene segments operably linked to mouse or human Cλ genes, wherein the one or more human Cλ genes are positioned at the site of a mouse Cλ gene, such that antibodies containing human Vλ and mouse or human Cλ domains can be expressed) are generally discussed herein, other non-human animals comprising a modified immunoglobulin kappa light chain locus are also provided. Such non-human animals include any animal that can be genetically modified to express antibodies as described herein, including, for example, mammals, such as mice, rats, rabbits, pigs, bovines (e.g., cattle, bulls, buffaloes), deer, sheep, goats, chickens, cats, dogs, ferrets, primates (e.g., marmosets, rhesus monkeys), and the like. For example, for non-human animals in which suitable genetically modified ES cells are not readily available, other methods are used to prepare non-human animals comprising such genetic modifications. Such methods include, for example, modifying the genome of a non-ES cell (e.g., a fibroblast or an induced pluripotent cell), transferring the genetically modified genome into a suitable cell, such as an enucleated oocyte, using somatic cell nuclear transfer (SCNT), and gestating the modified cell (e.g., a modified oocyte) in a non-human animal under suitable conditions to form an embryo. Methods for modifying the germline genome of a non-human animal (e.g., a pig, cow, rodent, chicken, etc. genome) include, for example, using zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), or Cas proteins (i.e., CRISPR / Cas systems) to include an engineered immunoglobulin kappa light chain locus as described herein. Guidance for methods of modifying the germline genome of a non-human animal can be found in, for example, U.S. Patent Application Nos. 14 / 747,461 (filed on June 23, 2015), 14 / 948,221 (filed on November 20, 2015), and 14 / 974,623 (filed on December 18, 2015); each of which is incorporated herein by reference in its entirety. In some embodiments, the non-human animals described herein are mammals. In some embodiments, the non-human animals described herein are small mammals, such as those of the Dipodoidea or Muroidea superfamily. In some embodiments, the genetically modified animals described herein are rodents. In some embodiments, the rodents described herein are selected from mice, rats, and hamsters. In some embodiments, the rodents described herein are selected from the Muroidea superfamily. In some embodiments, the genetically modified animals described herein are selected from the family Calomyscidae (e.g., mouse-like hamsters), the family Cricetidae (e.g., hamsters, New World rats and mice, voles), the family Muridae (true mice and rats, gerbils, spiny mice, crested rats), the family Nesomyidae (climbing mice, rock climbing mice, tailed rats, Madagascar rats, and mice), the family Platacanthomyidae (e.g., spiny dormice), and the family Spalacidae (e.g., moles, bamboo rats, and zokors). In certain embodiments, the genetically modified rodents described herein are selected from the family true mice or rats (Muridae), gerbils, spiny mice, and crested rats. In certain embodiments, the genetically modified mice described herein are members of the family Muridae. In some embodiments, the non-human animals described herein are rodents. In certain embodiments, the rodents described herein are selected from the family mice and rats. In some embodiments, the non-human animal described herein is a mouse. In some embodiments, the non-human animal described herein is a rodent that is a mouse C57BL strain selected from C57BL / A, C57BL / An, C57BL / GrFa, C57BL / KaLwN, C57BL / 6, C57BL / 6J, C57BL / 6ByJ, C57BL / 6NJ, C57BL / 10, C57BL / 10ScSn, C57BL / 10Cr, and C57BL / Ola. In certain embodiments, the mouse described herein is a 129-strain selected from the group consisting of strains 129P1, 129P2, 129P3, 129X1, 129S1 (e.g., 129S1 / SV, 129S1 / SvIm), 129S2, 129S4, 129S5, 129S9 / SvEvH, 129 / SvJae, 129S6 (129 / SvEvTac), 129S7, 129S8, 129T1, 129T2 (see, e.g., Festing et al., 1999, Mammalian Genome 10:836; Auerbach, W. et al., 2000, Biotechniques 29(5):1024-1028, 1030, 1032, each of which is herein incorporated by reference in its entirety). In certain embodiments, the genetically modified mice described herein are a mixture of the aforementioned 129 strain and the aforementioned C57BL / 6 strain. In certain embodiments, the mice described herein are a mixture of the aforementioned 129 strain, or a mixture of the aforementioned BL / 6 strain. In certain embodiments, the 129 strain in the mixed strain described herein is the 129S6 (129 / SvEvTac) strain. In certain embodiments, the mice described herein are a BALB strain, such as the BALB / c strain. In certain embodiments, the mice described herein are a mixture of the BALB strain and another of the aforementioned strains. In some embodiments, the non-human animal described herein is a rat. In certain embodiments, the rat described herein is selected from Wistar rats, LEA strain, Sprague Dawley strain, Fischer strain, F344, F6, and Dark Agouti. In certain embodiments, the rat strain described herein is a mixture of two or more strains selected from the group consisting of Wistar, LEA, Sprague Dawley, Fischer, F344, F6, and Dark Agouti. Rat pluripotent and / or totipotent cells can be derived from any rat strain, including, for example, the ACI rat strain (an inbred strain originally derived from the August and Copenhagen strains), the Dark Agouti (DA) rat strain, the Wistar rat strain, the LEA rat strain, the Sprague Dawley (SD) rat strain, or Fischer rat strains, such as the Fisher F344 or Fisher F6. Rat pluripotent and / or totipotent cells can also be derived from a mixture of two or more of the aforementioned strains. For example, rat pluripotent and / or totipotent cells can be derived from the DA strain or the ACI strain. The ACI rat strain is characterized by a black field mouse coloration, a white abdomen and feet, and the RT1av1 haplotype. These strains are available from a variety of sources, including Harlan Laboratories. An example of a rat ES cell line derived from the ACI rat is the ACI.G1 rat ES cell. The DA rat strain is characterized by an agouti coat and the RT1av1 haplotype. These rats are available from a variety of sources, including Charles River and Harlan Laboratories. Examples of rat ES cell lines derived from DA rats are the DA.2B rat ES cell line, and the DA.2C rat ES cell line. In some embodiments, rat pluripotent and / or totipotent cells are derived from inbred rat strains (see, e.g., U.S. Patent Application Publication No. 2014-0235933 A1, published on August 21, 2014, which is incorporated herein by reference in its entirety). Guidance for modifying the rat genome (e.g., in rat ES cells) using the methods and / or constructs described herein can be found in, e.g., U.S. Patent Application Publication Nos. 2014-0310828 and 2017-0204430; both of which are incorporated herein by reference in their entirety. Specific Illustrative Examples - Immunoglobulin Heavy Chain Locus In some embodiments, a non-human animal is provided that comprises a modified immunoglobulin kappa light chain locus as described herein, and further comprises a modified IgH locus (or allele) characterized by the presence of multiple human V H 、D H With J H Gene segments arranged in a germline configuration and operably linked to non-human immunoglobulin heavy chain constant region genes, enhancers, and regulatory regions. In some embodiments, the engineered immunoglobulin heavy chain loci (or alleles) described herein comprise one or more human V H Gene fragments, one or more human D H gene fragments and one or more human J H In certain embodiments, the engineered immunoglobulin heavy chain locus (or allele) comprises at least a human V H Gene segment V H 3-74, V H 3-73, V H 3-72, V H 2-70, V H 1-69, V H 3-66, V H 3-64, V H 4-61, V H 4-59, V H 1-58, V H 3-53, V H 5-51, V H 3-49, V H 3-48, V H 1-46, V H 1-45, V H 3-43, V H 4-39, V H 4-34, V H 3-33, V H 4-31, V H 3-30, V H 4-28, V H 2-26, V H 1-24, V H 3-23, V H 3-21, V H 3-20, V H 1-18, V H 3-15, V H 3-13, V H 3-11, V H 3-9, V H 1-8, V H 3-7, V H 2-5, V H 7-4-1, V H 4-4, V H 1-3, V H 1-2, V H 6-1, or any combination thereof. In certain embodiments, the engineered IgH locus (or allele) comprises at least human D H Gene fragment D H 1-1, D H 2-2, D H 3-3, D H 4-4, D H 5-5, D H 6-6, D H 1-7, D H 2-8, D H 3-9, D H 3-10, D H 5-12, D H 6-13, D H 2-15, D H3-16, D H 4-17, D H 6-19, D H 1-20, D H 2-21, D H 3-22, D H 6-25, D H 1-26, D H 7-27, or any combination thereof. In certain embodiments, the engineered immunoglobulin heavy chain locus (or allele) comprises at least human J H Gene fragment J H 1. J H 2. J H 3. J H 4. J H 5. J H 6, or any combination thereof. The present invention recognizes that the non-human animals described herein utilize human heavy chain variable region gene segments contained in their genomes in their antibody selection and production mechanisms (e.g., recombination and somatic hypermutation). Thus, in various embodiments, the human immunoglobulin heavy chain variable domains produced by the non-human animals described herein are encoded by human heavy chain variable region gene segments contained in their genomes or somatic hypermutators. In some embodiments, a non-human animal is provided, whose genome comprises a modified immunoglobulin kappa light chain locus, wherein the non-human animal comprises a B cell comprising a human heavy chain variable region sequence, a human lambda light chain variable region sequence, and / or a somatic hypermutated human kappa light chain variable region sequence. In some embodiments, the human heavy chain variable region sequence, human lambda light chain variable region sequence, and / or human kappa light chain variable region sequence present in the mouse B cells of the present invention have 1, 2, 3, 4, 5 or more somatic hypermutations. Methods for identifying source gene fragments in mature antibody sequences are known to those skilled in the art. For example, various tools can be used to assist in this analysis, for example, DNAPLOT, IMGT / V-QUEST, JOINSOLVER, SoDA, and Ab-origin. In some embodiments, the non-human immunoglobulin heavy chain constant region comprises one or more non-human immunoglobulin heavy chain constant region genes, such as immunoglobulin M (IgM), immunoglobulin D (IgD), immunoglobulin G (IgG), immunoglobulin E (IgE), and immunoglobulin A (IgA). In certain embodiments, the non-human immunoglobulin heavy chain constant region comprises rodent IgM, rodent IgD, rodent IgG3, rodent IgG1, rodent IgG2b, rodent IgG2a, rodent IgE, and rodent IgA constant region genes. In some embodiments, the human V H 、D H and J H gene segments operably linked to one or more non-human immunoglobulin heavy chain enhancers (i.e., enhancer sequences or enhancer regions). In some embodiments, the human V H 、D H and J H gene segment, operably linked to one or more non-human immunoglobulin heavy chain regulatory regions (or regulatory sequences). In some embodiments, the human V H 、D H and J H The gene segment is operably linked to one or more non-human immunoglobulin heavy chain enhancers (or enhancer sequences) and one or more non-human immunoglobulin heavy chain regulatory regions (or regulatory sequences). In some embodiments, the modified immunoglobulin heavy chain locus as described herein does not contain an endogenous Adam6 gene. In some embodiments, the modified immunoglobulin heavy chain locus as described herein does not contain an endogenous Adam6 gene (or Adam6 coding sequence) of the same germline genome as found in the germline genome of a wild-type non-human animal of the same species. In some embodiments, the modified immunoglobulin heavy chain locus as described herein does not contain a human Adam6 pseudogene. In some embodiments, the modified immunoglobulin heavy chain locus as described herein comprises the insertion of at least one nucleotide sequence encoding one or more non-human (e.g., rodent) Adam6 polypeptides, their functional homologs, functional homologs, or functional fragments. In some embodiments, the insertion may be located outside the modified immunoglobulin heavy chain locus as described herein (e.g., but not limited to, V Hgene fragment), within the engineered immunoglobulin heavy chain locus, or elsewhere in the non-human animal germline genome (for example, but not limited to, randomly introduced non-human Adam6 coding sequences), cells, or tissues. In various embodiments, a non-human animal, non-human cell, or non-human tissue as provided herein does not detectably express (in whole or in part) endogenous non-human V H In various embodiments, a non-human animal, non-human cell, or non-human tissue as provided herein does not contain (or lacks or contains deletions of) one or more nucleotide sequences that (in whole or in part) encode an endogenous non-human V region in an antibody molecule. H Region (e.g., V H 、D H , and / or J H In various embodiments, a non-human animal, non-human cell, or non-human tissue as provided herein has a germline genome comprising endogenous non-human V H 、D H and J H Deletion of a gene segment (full or partial). In various embodiments, the non-human animals provided are fertile. Guidance for creating targeting vectors, non-human cells, and animals carrying such engineered immunoglobulin heavy chain loci (or alleles) can be found in U.S. Patent Nos. 8,502,018, 8,642,835, 8,697,940, and 8,791,323, each of which is incorporated herein by reference in its entirety. A variety of techniques are known to those skilled in the art for achieving such genetic modification and / or manipulating the genome of a non-human animal (e.g., a mammal), or for preparing, providing, or manufacturing such sequences for introduction into the germline genome of a non-human animal. Specific Illustrative Examples - Immunoglobulin Kappa Light Chain Locus In some embodiments, non-human animals are provided that comprise an engineered immunoglobulin kappa light chain locus characterized by the presence of a plurality of human Vλ and Jλ gene segments arranged in a germline configuration (i.e., unrearranged and associated with a recombination signal sequence) and inserted and operably linked upstream of a non-human or human Cλ gene, wherein the non-human or human Cλ gene is inserted at the site of a non-human Cκ gene. As described herein, such engineered immunoglobulin kappa light chain loci further comprise a non-human immunoglobulin kappa light chain enhancer region (or enhancer sequence). In some embodiments, the engineered immunoglobulin kappa light chain locus comprises one or more human Vλ gene segments and one or more human Jλ gene segments operably linked to a non-human or human Cλ gene. In certain embodiments, the engineered immunoglobulin kappa light chain locus (or allele) comprises at least a human Vλ gene segment that occurs in cluster A of the human immunoglobulin lambda light chain locus; in some embodiments, cluster A and cluster B of the human immunoglobulin lambda light chain locus; in certain embodiments, cluster A, cluster B, and cluster C of the human immunoglobulin lambda light chain locus. In certain embodiments, the engineered immunoglobulin kappa light chain locus (or allele) comprises at least human Vλ gene segments Vλ4-69, Vλ8-61, Vλ4-60, Vλ6-57, Vλ10-54, Vλ5-52, Vλ1-51, Vλ9-49, Vλ1-47, Vλ7-46, Vλ5-45, Vλ1-44, Vλ7-43, Vλ8- In certain embodiments, the engineered Igκ light chain locus (or allele) comprises at least one of the human Jλ gene segments Jλ1, Jλ2, Jλ3, Jλ6, Jλ7, or any combination thereof. The present invention recognizes that the non-human animals described herein utilize human lambda light chain variable region gene segments contained in their genomes for their antibody selection and production mechanisms (e.g., recombination and somatic hypermutation). Thus, in various embodiments, the human immunoglobulin lambda light chain variable domains produced by the non-human animals described herein are encoded by human lambda light chain variable region gene segments contained in their genomes or in their somatic hypermutants. In some embodiments, a non-human animal is provided, whose genome comprises a modified immunoglobulin kappa light chain locus, wherein the non-human animal comprises a B cell comprising a human heavy chain variable region sequence, a human lambda light chain variable region sequence, and / or a somatic hypermutated human kappa light chain variable region sequence. In some embodiments, the human heavy chain variable region sequence, human lambda light chain variable region sequence, and / or human kappa light chain variable region sequence present in the mouse B cells of the present invention have 1, 2, 3, 4, 5 or more somatic hypermutations. Methods for identifying source gene fragments in mature antibody sequences are known to those skilled in the art. For example, various tools can be used to assist in this analysis, for example, DNAPLOT, IMGT / V-QUEST, JOINSOLVER, SoDA, and Ab-origin. In many embodiments, the engineered immunoglobulin κ light chain locus (or allele) contains the same non-human immunoglobulin κ light chain enhancer region (or enhancer sequence) as that found in a wild-type immunoglobulin κ light chain locus (or allele). In some embodiments, the engineered immunoglobulin κ light chain locus (or allele) contains a non-human immunoglobulin κ light chain enhancer region (or enhancer sequence) found in a wild-type immunoglobulin κ light chain locus (or allele) of a different species (e.g., a different rodent species). In some embodiments, the human Vλ and Jλ gene segments are operably linked to one or more non-human immunoglobulin κ light chain enhancers (i.e., enhancer sequences or enhancer regions). In certain embodiments, the human Vλ and Jλ gene segments are operably linked to a murine immunoglobulin κ light chain intronic enhancer region (Igκ Ei or Eiκ). In certain embodiments, the human Vλ and Jλ gene segments are operably linked to a murine immunoglobulin κ light chain 3' enhancer region (Igκ3'E or 3'Eκ). In certain embodiments, the human Vλ and Jλ gene segments are operably linked to a murine Eiκ and operably linked to murine 3'Eκ. In some embodiments, the engineered immunoglobulin kappa light chain locus (or allele) described herein does not contain (ie, lacks) a human VpreB gene (or a human VpreB gene coding sequence). In some embodiments, the non-human Cλ gene of the engineered immunoglobulin κ light chain locus (or allele) comprises a rodent Cλ gene, such as a mouse Cλ gene or a rat Cλ gene. In certain embodiments, the non-human Cλ gene of the engineered Ig κ light chain locus (or allele) is or comprises a mouse Cλ gene from a genetic background including a 129 strain, a BALB / c strain, a C57BL / 6 strain, a mixed 129xC57BL / 6 strain, or a combination thereof. In some embodiments, the non-human Cλ gene of the engineered Igκ light chain locus (or allele) described herein comprises a sequence that is at least 80%, at least 85%, at least 90%, at least 95%, or at least 98% identical to SEQ ID NO: 1 (mouse Cλ1), SEQ ID NO: 3 (mouse Cλ2), or SEQ ID NO: 5 (mouse Cλ3). In some embodiments, the non-human Cλ gene of the engineered Igκ light chain locus (or allele) described herein comprises a sequence that is substantially identical to or equivalent to SEQ ID NO: 1 (mouse Cλ1), SEQ ID NO: 3 (mouse Cλ2), or SEQ ID NO: 5 (mouse Cλ3). In some embodiments, the non-human Cλ gene of the engineered Igκ light chain locus (or allele) described herein is or comprises the sequence of a mouse Cλ1 gene. In some embodiments, the non-human Cλ gene of the engineered Igκ light chain locus (or allele) described herein comprises a sequence that is at least 80%, at least 85%, at least 90%, at least 95%, or at least 98% identical to SEQ ID NO: 2 (mouse Cλ1), SEQ ID NO: 4 (mouse Cλ2), or SEQ ID NO: 6 (mouse Cλ3). In some embodiments, the non-human Cλ gene of the engineered Igκ light chain locus (or allele) described herein comprises a sequence that is substantially identical to or equivalent to SEQ ID NO: 2 (mouse Cλ1), SEQ ID NO: 4 (mouse Cλ2), or SEQ ID NO: 6 (mouse Cλ3). In some embodiments, the non-human Cλ gene encoded by the sequence located in the engineered Igκ light chain locus (or allele) described herein is or comprises a mouse Cλ1 domain polypeptide. In some embodiments, the non-human Cλ gene of the engineered Igκ light chain locus (or allele) as described herein comprises a sequence that is at least 80%, at least 85%, at least 90%, at least 95%, or at least 98% identical to SEQ ID NO: 7 (rat Cλ1), SEQ ID NO: 9 (rat Cλ2), SEQ ID NO: 11 (rat Cλ3), or SEQ ID NO: 13 (rat Cλ4). In some embodiments, the non-human Cλ gene of the engineered Igκ light chain locus (or allele) as described herein comprises a sequence that is substantially identical to or equivalent to SEQ ID NO: 7 (rat Cλ1), SEQ ID NO: 9 (rat Cλ2), SEQ ID NO: 11 (rat Cλ3), or SEQ ID NO: 13 (rat Cλ4). In certain embodiments, the non-human Cλ gene of the engineered Igκ light chain locus (or allele) as described herein is or comprises the sequence of a rat Cλ1 gene. In some embodiments, the non-human Cλ gene of the engineered Igκ light chain locus (or allele) described herein comprises a sequence that is at least 80%, at least 85%, at least 90%, at least 95%, or at least 98% identical to SEQ ID NO: 8 (rat Cλ1), SEQ ID NO: 10 (rat Cλ2), SEQ ID NO: 12 (rat Cλ3), or SEQ ID NO: 14 (rat Cλ4). In some embodiments, the non-human Cλ gene of the engineered Igκ light chain locus (or allele) described herein comprises a sequence that is substantially identical or equivalent to SEQ ID NO: 8 (rat Cλ1), SEQ ID NO: 10 (rat Cλ2), SEQ ID NO: 12 (rat Cλ3), or SEQ ID NO: 14 (rat Cλ4). In some embodiments, the non-human Cλ gene encoded by the sequence located at the engineered Igκ light chain locus (or allele) described herein is or comprises a rat Cλ1 domain polypeptide. In some embodiments, the human Cλ gene of the modified Igκ light chain locus (or allele) includes a human Cλ gene, such as a human Cλ1 gene, a human Cλ2 gene, a human Cλ3 gene, a human Cλ6 gene, or a human Cλ7 gene. In certain embodiments, the human Cλ gene of the modified Igκ light chain locus (or allele) is or includes a human Cλ2 gene. In some embodiments, the human Cλ gene of the engineered Igκ light chain locus (or allele) as described herein comprises a sequence that is at least 80%, at least 85%, at least 90%, at least 95%, or at least 98% identical to SEQ ID NO: 15 (human Cλ1), SEQ ID NO: 17 (human Cλ2), SEQ ID NO: 19 (human Cλ3), SEQ ID NO: 21 (human Cλ6), or SEQ ID NO: 23 (human Cλ7). In some embodiments, the human Cλ gene of the engineered Igκ light chain locus (or allele) as described herein comprises a sequence that is substantially identical to or equivalent to SEQ ID NO: 15 (human Cλ1), SEQ ID NO: 17 (human Cλ2), SEQ ID NO: 19 (human Cλ3), SEQ ID NO: 21 (human Cλ6), or SEQ ID NO: 23 (human Cλ7). In some embodiments, the human Cλ gene of the engineered Igκ light chain locus (or allele) as described herein is or comprises the sequence of a human Cλ2 gene. In some embodiments, a human Cλ domain encoded by a sequence located in an engineered Igκ light chain locus (or allele) described herein comprises a sequence that is at least 80%, at least 85%, at least 90%, at least 95%, or at least 98% identical to SEQ ID NO: 16 (human Cλ1), SEQ ID NO: 18 (human Cλ2), SEQ ID NO: 20 (human Cλ3), SEQ ID NO: 22 (human Cλ6), or SEQ ID NO: 24 (human Cλ7). In some embodiments, a human Cλ domain encoded by a sequence located in an engineered Igκ light chain locus (or allele) described herein comprises a sequence that is substantially identical to or equivalent to SEQ ID NO: 16 (human Cλ1), SEQ ID NO: 18 (human Cλ2), SEQ ID NO: 20 (human Cλ3), SEQ ID NO: 22 (human Cλ6), or SEQ ID NO: 24 (human Cλ7). In some embodiments, the human Cλ domain encoded by a sequence located at an engineered Igκ light chain locus (or allele) as described herein is or comprises a human Cλ2 domain polypeptide. Among other things, the present disclosure demonstrates that the presence of human Vλ and Jλ gene segments at an Igκ light chain locus (or allele) can increase the diversity of the light chain repertoire provided, compared to the light chain diversity in the antibody repertoire displayed by a non-human animal that does not contain such an engineered Igκ light chain locus. Specific Illustrative Example - Immunoglobulin Lambda Light Chain Locus In some embodiments, a non-human animal is provided that comprises an engineered immunoglobulin kappa light chain locus as described herein, and further comprises a wild-type or inactivated immunoglobulin lambda light chain locus (or allele). In some embodiments, the non-human animals, non-human cells, and / or non-human tissues provided herein comprise deletions (in whole or in part) of an endogenous immunoglobulin lambda light chain locus. In some embodiments, the non-human animals, non-human cells, and / or non-human tissues provided herein comprise insertions into an endogenous immunoglobulin lambda light chain locus, wherein the insertions render the endogenous immunoglobulin lambda light chain locus nonfunctional. In some embodiments, the non-human animals, non-human cells, and / or non-human tissues provided herein comprise deletions of one or more gene segments of an endogenous immunoglobulin lambda light chain locus, rendering the endogenous immunoglobulin lambda light chain locus incapable of recombination and / or expression of functional light chains for antibodies. I...

Claims

1. A method for manufacturing genetically modified mice, the method comprising the steps of: modifying the first endogenous immunoglobulin κ light chain locus in the germline genome of the mouse to include: (i) one or more human Vλ gene fragments, (ii) one or more human Jλ gene fragments, and (iii) a mouse Cλ gene, wherein the one or more human Vλ gene fragments in (i) and the one or more human Jλ gene fragments in (ii) are operatively linked to the mouse Cλ gene in (iii), wherein the mouse Cλ gene in (iii) replaces the mouse Cκ gene at the first modified endogenous immunoglobulin κ light chain locus; wherein the one or more human Vλ gene fragments in (i) and the one or more human Jλ gene fragments in (ii) replace one or more endogenous mouse Vκ gene fragments and one or more endogenous mouse Jκ gene fragments; and wherein the genetically modified mouse lacks the mouse Cκ gene at the first modified endogenous immunoglobulin κ light chain locus.

2. The method as described in claim 1, wherein the first modified endogenous immunoglobulin κ light chain locus of the genetically modified mouse is homozygous.

3. The method as described in claim 1, wherein the first modified endogenous immunoglobulin κ light chain locus of the genetically modified mouse is heterozygous.

4. The method as described in claim 3, wherein the method further comprises the step of: modifying a second modified endogenous immunoglobulin κ light chain locus in the germline genome of the mouse to include: (a) one or more human Vκ gene fragments, and (b) one or more human Jκ gene fragments, wherein the one or more human Vκ gene fragments and the one or more human Jκ gene fragments are operatively linked to the Cκ gene.

5. The method as claimed in claim 1, wherein the method further comprises the step of: modifying the modified endogenous immunoglobulin heavy chain locus in the germline genome of the mouse to include: (a) one or more human VH gene fragments, (b) one or more human DH gene fragments, and (c) one or more human JH gene fragments, wherein the one or more human VH gene fragments in (a), the one or more human DH gene fragments in (b), and the one or more human JH gene fragments in (c) are operatively linked to one or more mouse immunoglobulin heavy chain constant region genes at the modified endogenous immunoglobulin heavy chain gene locus.

6. The method as described in claim 5, wherein (a) the one or more human VH gene fragments, (b) the one or more human DH gene fragments, and (c) the one or more human JH gene fragments are located at one or more mouse VH gene fragments, one or more mouse DH gene fragments, one or more mouse JH gene fragments, or a combination thereof.

7. The method as described in claim 5 or 6, wherein the modified endogenous immunoglobulin heavy chain locus further comprises: (i) one or more human VH non-coding sequences, each of which is adjacent to at least one of the one or more human VH gene segments, wherein each of the one or more VH non-coding sequences is naturally occurring in a human VH gene segment adjacent to the endogenous human immunoglobulin heavy chain locus; (ii) one or more human DH non-coding sequences, each of which is adjacent to at least one of the one or more human DH gene segments, wherein each of the one or more DH non-coding sequences is naturally occurring in a human DH gene segment adjacent to the endogenous human immunoglobulin heavy chain locus; (iii) one or more human JH non-coding sequences, each of which is adjacent to at least one of the one or more human JH gene segments, wherein each of the one or more JH non-coding sequences is naturally adjacent to a human JH gene segment adjacent to the endogenous human immunoglobulin heavy chain locus; or (iv) Any combination thereof.

8. The method as described in claim 5 or 6, wherein the one or more mouse immunoglobulin heavy chain constant region genes are one or more endogenous mouse immunoglobulin heavy chain constant region genes.

9. The method as described in claim 5 or 6, wherein: (i) The one or more human VH gene fragments include VH3-74, VH3-73, VH3-72, VH2-70, VH1-69, VH3-66, VH3-64, VH4-61, VH4-59, VH1-58, VH3-53, VH5-51, VH3-49, VH3-48, VH1-46, VH1-45, VH3-43, VH4-39, VH4-34, V H3-33, VH4-31, VH3-30, VH4-28, VH2-26, VH1-24, VH3-23, VH3-21, VH3-20, VH1-18, VH3-15 , VH3-13, VH3-11, VH3-9, VH1-8, VH3-7, VH2-5, VH7-4-1, VH4-4, VH1-3, VH1-2, VH6-1, or combinations thereof, (ii) The one or more human DH gene fragments comprise DH1-1, DH2-2, DH3-3, DH4-4, DH5-5, DH6-6, DH1-7, DH2-8, DH3-9, DH3-10, DH5-12, DH6-13, DH2-15, DH3-16, DH4-17, DH6-19, DH1-20, DH2-21, DH3-22, DH6-25, DH1-26, DH7-27, or combinations thereof, and (iii) The one or more human JH gene fragments comprise JH1, JH2, JH3, JH4, JH5, JH6, or combinations thereof.

10. The method as described in claim 5 or 6, wherein the modified endogenous immunoglobulin heavy chain locus of the genetically modified mouse is homozygous.

11. The method as described in any one of claims 1 to 6, wherein (i) the one or more human Vλ gene fragments and (ii) the one or more human Jλ gene fragments are substitutes for the one or more mouse Vκ gene fragments, the one or more mouse Jκ gene fragments, or a combination thereof.

12. The method as described in any one of claims 1 to 6, wherein the first modified endogenous immunoglobulin κ light chain locus further comprises a κ light chain non-coding sequence between one or more human Vλ gene segments and one or more human Jλ gene segments.

13. The method as described in claim 12, wherein the κ light chain non-coding sequence has a sequence that naturally occurs between a human Vκ4-1 gene fragment and a human Jκ1 gene fragment at the endogenous human immunoglobulin κ light chain locus.

14. The method as described in any one of claims 1 to 6, wherein the endogenous Vλ gene fragment, the endogenous Jλ gene fragment, and the endogenous Cλ gene are all or partly deleted.

15. The method of any one of claims 1 to 6, wherein each of the human light chain variable domains is encoded by a rearranged human immunoglobulin λ light chain variable region sequence comprising (i) one or more human Vλ gene segments, or a highly mutated variant thereof in somatic cells, and (ii) one or more human Jλ gene segments, or a highly mutated variant thereof in somatic cells.

16. The method as described in any one of claims 1 to 6, wherein the germline genome further comprises a nucleic acid sequence encoding an exogenous terminal deoxynucleotidyl transferase (TdT) operatively linked to the transcription control unit.

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