Memory b-cell precursor cells and uses thereof

A technology of precursor cells and B cells, applied in the direction of animal cells, vertebrate cells, cell culture active agents, etc., can solve the problems of memory B cells that need to be further studied

Active Publication Date: 2019-11-22
TSINGHUA UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] However, the formation of memory B cells remains to be further studied

Method used

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  • Memory b-cell precursor cells and uses thereof
  • Memory b-cell precursor cells and uses thereof
  • Memory b-cell precursor cells and uses thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0174] Example 1 Identification of transitional state subgroups in germinal center B cells

[0175] In this example, the inventors introduced in detail the transition state subset of germinal center B cells-memory B cell precursor cells mKO2 hi identification process and results.

[0176] In order to identify isolated non-dividing GC B cells, the inventors constructed a cell cycle fluorescent indicator mouse UBP-2A-Fucci (Sakaue-Sawano, A., et al. (2008). "Visualizing spatiotemporaldynamics of multicellular cell- cycle progression." Cell 132(3):487-498.), the mouse can express the red fluorescent protein mKO2 in the resting G0 / G1 phase of the cell cycle, and express the green protein mAG in the G2 / S / M phase of the division phase. The inventors used NP-KLH (NP is a hapten linked to a large protein such as KLH as an immunogen, and NP is a very commonly used immune method, which can be determined by tracking BCR (B cell receptor) for NP antigen specificity) to intraperitoneal ...

Embodiment 2

[0180] Example 2 CD19 + GL7 + Fas + CD38 + Bcl6 - mKO2 hi precursor of memory B cells

[0181] In this example, the inventors verified that CD19 + GL7 + Fas + CD38 + Bcl6 - mKO2 hi (abbreviated as mKO2 hi CD38 + ) cells have the potential to differentiate into memory B cells.

[0182] Considering CD19 + GL7 + Fas + CD38 + Bcl6 - mKO2 hi Transitional GC cell subsets are in the G0 phase of the cell cycle, so they must be derived from mKO2 in the G1 phase of GC cells lo CD38 - GL7 + FAS + cells, and are likely to be preparing to differentiate into memory B cells. In order to further explore the characteristics of this group of transitional GC B cells and their developmental pathways, the inventors used RNA deep sequencing to analyze the gene expression profiles of this subpopulation and its corresponding G1 phase GC cells. Since this population of transitional cells constitutes an extremely small proportion (approximately 5% of GCs), the inventors optimize...

Embodiment 3

[0187] Example 3 Interleukin-9 (IL-9) promotes the development of GC-MP cells and the differentiation to memory B cells

[0188] In order to identify extracellular factors that promote the development and differentiation of GC-MP, the inventors further analyzed the sequencing data using bioinformatics methods, hoping to obtain some clues and hints. The inventor compared the signaling pathways of differentially expressed gene enrichment between GC-MP cells and GC-MPP cells by gene set enrichment analysis (GSEA), wherein the JAK-STAT signaling pathway has aroused great interest of the inventors (the results are as follows: Figure 5a shown), implying that GC-MP cells have special features with GC-MPP in the JAK-STAT pathway, or that the pathway promotes the formation of GC-MP by GC-MPP, or that the pathway has a function on GC-MP itself and subsequent differentiation play an important role. On the other hand, since there is no direct correlation between transcription factor mRN...

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Abstract

The invention provides a memory B cell precursor cell and use thereof. The memory B cell precursor cell has the following marker: CD19<+>GL7<+>Fas<+>Bcl6<->, preferably for marker CD38, the memory B cell precursor cell has an expression level opposite to a germinal center, and optionally the memory B cell precursor cell is G0 phase cell. And the memory B cell precursor cell has the potential of differentiation into memory B cells.

Description

technical field [0001] The present invention relates to the field of biology. Specifically, the present invention relates to memory B cell precursor cells and uses thereof. More specifically, the present invention relates to memory B cell precursor cells, methods for obtaining memory B cell precursor cells, and methods for promoting memory B cell A method for transforming precursor cells into memory B cells, a method for inhibiting the transformation of memory B cell precursor cells into memory B cells, the use of reagents in preparing medicines, a method for obtaining memory B cells and a vaccine. Background technique [0002] When the body is infected by external pathogens, the immune system will initiate a series of protective mechanisms to resist the invasion of pathogens, including innate immunity and acquired immunity. Some specific pathogens can be cleared simply only through the innate immune mechanism, while the vast majority of pathogens will break through the inna...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12N5/0781A61K38/20A61K45/00A61K35/17A61K39/145A61P25/28
CPCA61K35/17A61K38/206A61K39/12A61K45/00C12N5/0635C12N2501/2309C12N2501/999C12N2760/16134A61K2300/00
Inventor 祁海王毅峰史静雯晏家骢侯小筱
Owner TSINGHUA UNIV
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