Use of il-12 related biomarkers and il-12 specific blocking antibodies for the treatment of an autoimmune disease

Abstract

Methods are disclosed for treating a subject with an autoimmune disease. These methods include selecting a subject with the autoimmune disease that has i) an increase in ABC, DN1 cells, DN2 cells, DN3 cells and / or plasmablasts in a blood sample obtained from the subject as compared to control subjects, and / or ii) an increase of T-bet, CXCR3, CD326, VISTA, Ly6H, CD317 and / or IFNγ expressing lymphocytes as compared to a control; iii) elevated serum concentration of IL-12 and / or IFNγ as compared to a control, and / or iv) elevated anti-RNA or anti-SM antibodies as compared to a control, and administering to the subject an effective amount of IL-12 antagonist. Methods are disclosed for selecting a subject with an autoimmune disease that can be treated with an IL-12 antagonist. In some aspects, the autoimmune disease is systemic lupus erythematosus (SLE) or Sjogren's syndrome. Compositions including a therapeutically effective of an IL-12 antagonist for use in these methods are also disclosed.

Description

[0001]USE OF IL-12 RELATED BIOMARKERS AND IL-12 SPECIFIC BLOCKING ANTIBODIES FOR THE TREATMENT OF AN AUTOIMMUNE DISEASE CROSS REFERENCE TO RELATED APPLICATIONS This claims the benefit of U.S. Provisional Patent Application No.63 / 528,166, filed July 21, 2023, which is incorporated herein by reference. STATEMENT OF GOVERNMENT SUPPORT This invention was made with government support under AI089443 awarded by the National Institutes of Health. The government has certain rights in the invention. FIELD OF THE DISCLOSURE This relates to the field of autoimmune disease, specifically to the use of interleukin (IL)-12 related biomarkers to identify subjects with an autoimmune disease as suitable for treatment with IL-12 antagonists, and to the treatment of these subject. BACKGROUND A number of chemical and biological immunotherapeutic methods have been developed for treating autoimmune disorders. Typically, immunotherapeutic methods have attempted to treat autoimmune disorders after they have begun by dampening the entire immune response using, e.g., chemical agents such as steroids or anti-immune cell antibodies. For example, one such method attempts to treat autoimmune disorders by administering antibodies that bind to B-cell antigens, e.g., CD22, CD20, CD19, and CD74 or HLA-DR antigen. A need remains for methods to identify subjects with an autoimmune disease that can be treated using an immunotherapeutic method, and for methods for treating the identified subjects. SUMMARY OF THE DISCLOSURE Methods are disclosed for treating a subject with an autoimmune disease. These methods include selecting a subject with the autoimmune disease that has: i) an increase in ABC, DN1 cells, DN2 cells, DN3 cells and / or plasmablasts in a biological sample obtained from the subject as compared to control subjects, ii) an increase of T-bet, CXCR3, CD326, V-domain Ig suppressor of T cell activation (VISTA), Ly6H CD317 and / or IFNγ expressing lymphocytes in a biological sample obtained from the subject as compared to a control; iii) elevated serum concentration of IL-12 and / or IFNγ as compared to a control, and / or iv) elevated anti-RNA or anti-SM antibodies in a biological sample obtained from the subject as compared to a control. These methods also include administering to the subject an effective amount of IL-12 antagonist, thereby treating the autoimmune disease in the subject. Methods are disclosed for selecting a subject with an autoimmune disease that can be treated with an IL-12 antagonist. These methods include detecting i) an increase in DN1 cells, DN2 cells, DN3 cells and / or plasmablasts in a biological sample obtained from the subject as compared to control subjects, ii) an increase of T-bet, CXCR3, CD326, VISTA, Ly6H, CD317 and / or IFNγ expressing lymphocytes in a biological sample obtained from the subject as compared to a control; iii) elevated serum concentration of IL-12 and / or IFNγ as compared to a control, and / or iv) elevated anti-RNA or anti-SM antibodies in a biological sample obtained from the subject as compared to a control. The foregoing and other features and advantages of the invention will become more apparent from the following detailed description of several aspects which proceeds with reference to the accompanying figures. BRIEF DESCRIPTION OF THE FIGURES FIGs.1A-1F. IL-12 signaling on either B cells or CD4 T cells is sufficient to suppress GC. FIGs. 1A-1C: B6 or IL12Rb2 KO B6 mice were immunized intraperitoneally with NP-CGG in alum, then 3-4 hours later injected with either heat killed control (HK Ctl) or live Salmonella (infected) intraperitoneally, and their splenocytes analyzed 12 days later. FIG.1A: Representative pseudoplots pre-gated on [live, singlets, TCRb-], showing gates for NIP+ CD19+ B cells (NP-specific), then CD38lowCD95hiGC. Numbers next to gated regions indicate percentages of cells from the parent gate. FIG.1B: Number of NIP+ GCBC per spleen from two independent experiments pooled for all but Ctl WT, which was from one experiment, as this condition has been previously published (Elsner et al., 2019, Cell Rep 29: 2796-2809). One-way ANOVA with Tukey’s multiple comparisons, n=3-6 per group per experiment. FIG.1C: Number of STm colony forming units (CFU) per spleen from two experiments pooled. Two-tailed Student’s t test. FIG.1D: Experimental design for panels FIG.1E and FIG.1F. CD4+ T cells and B cells were purified by depletion of unwanted cells with magnetic beads and recombined into 4 mixtures, which were then injected into OTII+ / - Rag2KO CD45.1 / 2 hosts at day -1. Recipients were immunized with NP-CGG and injected with HK Ctl or infected with STm at day 0, and their splenocytes were assessed 12 days later. FIG.1E: Number of GC per spleen from two experiments pooled, n=3-5 per group per experiment. One-way ANOVA with Tukey’s multiple comparisons. FIG.1F: Representative FACS plots pre-gated on [live, singlet, TCRb-, CD19+] and CD45.1 / 1 or CD45.2 / 2 to ensure the origin of the B cells, as indicated. For all charts, points represent individual mice and bars the mean + / - SD. NS = not significant, *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001. FIGs.2A-2D. IL-12 signaling on either B cells or CD4 T cells is sufficient to suppress GC. FIG. 2A: Gating scheme to identify NP-specific (NIP+) germinal center B cells for FIG.1A, example shown is from HK STm control group. FIG.2B: C57Bl / 6 mice were infected with STm (Inf) or injected with HK bacteria control (Ctl), 3 days later immunized with NP-CGG, and spleens analyzed 12 days later. Comparison of the percentage of NP-specific B cells that are GC phenotype 12 days post NP-CGG immunization. Symbols represent individual mice pooled from 2 experiments, n=3-6 per group per experiment, One-way ANOVA with Tukey’s multiple comparisons, NS=not significant, *p<0.01. FIG.2C: Gating scheme used to identify donor derived B cells and germinal centers for FIGs.1E-1F, example shown is from HK STm control group with WT B cell donor. FIG.2D: Example upstream gating plots for FIGs. 1E-1F to show gating of donor B cells for CD45.1 and CD45.2 genotypes. FIGs.3A-3C. IL-12 signaling in B cells is necessary and sufficient to promote PB differentiation. FIG.3A: B6 mice with an irrelevant BCR (B18+ / - Vk8R+ / - CD45.1 / 2) were irradiated and reconstituted with a mixture of 50% WT CD45.1 and 50% IL12Rb2 KO CD45.2 bone marrow. After 10 weeks, mice were infected with STm or given HK bacteria and 3 days later immunized with NP-CGG, then analyzed at 12 days post NP-CGG immunization. Shown are representative FACS plots of reconstitution among resting T cells (CD4+ CD44low), resting B cells (CD19+ CD38hiCD95lowCD138- CD44low), and plasmablasts (TCRb- CD138+ CD44hi). Numbers in parentheses are the ratio of %WT / %KO per mouse. FIG.3B: Ratios of %WT / %KO were used to normalize competitive advantage for each mouse of resting B cells relative to resting T cells (left), and to calculate the competitive advantage for IL12Rb2 expression among PB relative to resting B cells (right). Values >1 indicate the fold-advantage of WT cells. One-way ANOVA was used to compare groups for resting B cells (left), and Student’s t-test was used to compare HK and Infected groups for PB competitive advantage. Additionally, one-sample t-tests are displayed at the top of each chart in parentheses to compare each group individually to the hypothetical value of 1 for “no competitive advantage”(*)p<0.0332,(**)p<0.0021,(***)p<0.0002,(****)p<0.0001). Symbols indicate individual mice, bars the mean + / - SD. Data are pooled from 2 experiments, n=4-5 per group for HK and Inf, n=2 for naïve. FIG.3C: WT B6 mice were immunized with NP-CGG, then PBS or 800 ng recombinant IL-12 was administered intravenously on days 1, 2, and 3 post immunization. At day 4 splenic antibody secreting cells were quantified by ELISPOT, and the number of NIP+ CD138+ PB and the %IgM+ of CD138+ PB were determined by flow cytometry. Data are pooled from two experiments, n=5 per group per experiment, analyzed with one-tailed t tests. For all charts symbols represent individual mice, bars the mean + / - SD. NS = not significant, *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001. FIGs.4A-4D. Example calculation for competitive advantage in mixed bone marrow chimeras. FIG.4A: Example gating scheme to identify resting T cells (CD4+CD44lowPD-1-), resting B cells (CD19+NIP- CD38highCD95low), and plasmablasts (CD138+ CD44hi). Example is from chimera treated with HK- STm and NP-CGG as described in FIGs.3A-3C. FIG.4B: Example FACS plots to be used to demonstrate calculations, same as FIG.4A. Data are summarized below, showing paired comparisons of the CD45.1 / CD45.2 ratio for resting T cells or B cells from the same mouse. Symbols indicate individual mice pooled from 2 experiments n=4-5 per group per experiment except naïve where n=2, paired Student’s t-test was used to compare resting T and B cells for each treatment. FIG.4C. Example calculation to normalize resting B cell reconstitution on a per mouse basis. Resting B cells show a disadvantage for WT cells (30% WT vs 69% KO) compared to T cells, which show equal competition (48% WT vs 45% KO) after reconstituting irradiated mice with 50% / 50% mixture of WT and IL12RKO bone marrow donor cells. Normalization to the resting T ratio gives a value <1 which indicates KO advantage. FIG.4D. Example calculation normalizing PB to resting B cells to account for WT disadvantage in reconstitution. When accounting for the WT disadvantage of resting B cell reconstitution (30% WT vs 69% KO), PB show WT advantage (44% WT vs 45% KO) giving a normalized value >1 (2.23). FIG.5A-5B. IL-12 promotes both proliferation and differentiation of purified B cells in vitro. FIGs. 5A-5B: B cells from IL12p40 KO B6 mice were purified by magnetic depletion of unwanted cells, labeled with violet proliferation dye (VPD), and cultured for 4 days with LPS stimulation with graded concentrations of recombinant murine IL-12, then analyzed by flow cytometry. FIGs.5A: Top: an overlay histogram of live singlet B cells from indicated culture conditions. Center: the % of cells that underwent at least one division (%Divided); and bottom: the average number of divisions of dividing cells (Proliferation index) were calculated with the FlowJo Proliferation Platform. Points and error bars are the mean + / - SD from 3 mice cultured individually. One experiment representative of three is shown. Effect of IL-12 concentration was determined by One-way ANOVA with Dunnett’s multiple comparisons for each point compared to 0 pg / mL IL-12. FIG.5B: Analysis of the effect of IL-12 on differentiation of cells from FIG. 5A. The number of cell divisions was determined by gating on each proliferation peak, then the % of Blimp- 1+ CD138+ cells (plasmablasts) among each division number was plotted in triplicate (mean + / - SD). Colors represent individual IL-12 concentrations, and 2-way ANOVA with Dunnett’s multiple comparisons was used to compare each concentration to 0 pg / mL IL-12. *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001. FIGs.6A-6E. IL-12 promotes both proliferation and differentiation from B cells in vitro. FIG.6A: Bead purified IL12p40 KO B cells were cultured for 4 days with LPS + recombinant IL-12 at the indicated concentrations, then analyzed by flow cytometry. Gating scheme used for analysis of proliferation and plasmablast (Blimp-1+ CD138+) differentiation among live B cells in FIGs.6A-6B. An example of Blimp-1 and CD138 expression among total B cells is shown for reference, and that gate was applied to all VPD peaks individually with examples shown for cells in division peak 1 and 4. An example of FlowJo Proliferation Platform analysis is shown in the bottom left. FIG.6B Extended titration of IL-12 on LPS stimulated cells with analysis at 3 and 4 days without Blimp-1 staining. The frequency of live CD138+ VPDlow(excluding undivided cells) was determined by flow cytometry (left), the number of live cells per well were enumerated using trypan blue stain (center), and the two were used to calculate the number of live CD138+ VPDlowcells per well in each condition. Data are individual mice pooled from two experiments for n=2 for each culture time point, shown are mean + / - SD. FIGs.6C-6E: Bead purified IL12p40 KO B cells were cultured for 4 days with CpG ODN1826 + recombinant IL-12 and analyzed by flow cytometry. Data are individual mice pooled from 2 experiments for n=2, shown are mean + / - SD. FIG.6C: Example of proliferation dye dilution by histogram overlay, and %Divided and Proliferation index as above, with One- way ANOVA and Dunnett’s multiple comparisons to 0 pg / mL IL-12. FIG.6D: Analysis of differentiation per division number, as described for FIG.5B with 2-way ANOVA and Dunnett’s multiple comparisons comparing each group to 0 pg / mL IL-12. FIG.6E: example FACS plots of %Blimp-1+ CD138+ cells in indicated culture conditions. FIGs.7A-7D. IL-12-induced production of IFNγ by B cells promotes PB differentiation via autocrine signaling. FIGs.7A-7C: B cells of the indicated genotypes were cultured with LPS + / - recombinant IL-12 for 4 days. Flow cytometry plots show representative samples of IL12p40 KO cells cultured with 0 and 200 pg / mL IL-12, gated on live singlet B cells. Charts to the right show summary data from all genotypes. FIG.7A: Quantitation of Blimp-1hiCD138+PB. FIG.7B: Quantitation of Blimp-1hiIRF4hicells. FIG.7C: Quantitation of Blimp-1loT-bethicells. Data are pooled from 3 experiments with a total of 2-3 replicates per genotype, symbols indicate the mean + / - SD. Statistical analysis by 2-way ANOVA with Tukey’s multiple comparison. FIG.7D: B cells of the indicated genotypes were cultured with LPS with dose titrations of recombinant IL-12 (left) and IFNγ (right). Percentages of Blimp-1hiCD138+PB as gated in FIG.7A are plotted as a function of cytokine concentration. Data are pooled from 3 experiments for n=3 per genotype, symbols indicate the mean + / - SD. Statistical analysis by 2-way ANOVA with Dunnett’s multiple comparison. *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001. FIGs.8A-8E. IL-12 induces B cell production of IFNγ that promotes PB differentiation through autocrine signaling. FIG.8A: Comparison of WT and IL12p40 KO B cells for Blimp-1+ CD138+ cell differentiation among proliferation peaks after four days of stimulation in the presence of LPS + / - recombinant IL-12, or IL-12 blocking antibody. Data are pooled from 3 experiments for a total of 4 replicates per genotype. Statistical analyses are 2-way ANOVA. FIGs.8B-8E: Four-day LPS stimulation of bead purified B cells comparing dose titrations of recombinant IL-12 and IFNγ on both IL12p40 KO and IFNγ KO B cells. Data are pooled from 3 experiments for n=3 per genotype. All symbols represent mean + / - SD, *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001. FIG.8B: Representative FACS plots of proliferation dye dilution between groups. FIG.8C: Precursor frequency of cells that have divided at least once (%Divided), and FIG.8D: the average number of divisions of dividing cells (Proliferation index) as calculated by FlowJo proliferation analysis. Statistical analysis is 2-way ANOVA with Dunnett’s multiple comparison comparing each concentration to controls of 0 pg / mL IL-12 or 0 ng / mL IFNγ and comparing IL12p40 KO cells to IFNγ KO cells. FIG.8E: Analysis of Blimp-1+ CD138+ cell differentiation among divisions comparing titration of IL-12 (left) or IFNγ (right) on IL12p40 KO (square symbols solid lines) or IFNγ KO (triangle symbols dotted lines) B cells. Statistical analysis is 2-way ANOVA with Tukey’s multiple comparison. FIGs.9A-9I. Effects of IFNγ responsiveness and T-bet expression on PB responses in vivo and in vitro. FIGs.9A-9D: CD19Cre+ / -IFNgR1flox / floxB6 mice (B-KO), or Cre-negative IFNgR1flox / floxcontrols (B- WT) were infected with Salmonella (Inf) or given heat killed bacteria control (HK), then immunized 3 days later with NP-CGG, then analyzed 5 days after NP-CGG immunization. Data are pooled from 2 independent experiments, n=5-8 mice per group for each experiment. For FIGs.9A-9C, symbols represent individual mice and bars the mean + / - SD, statistics indicate t-test comparing B-WT to B-KO of either control or infected groups,*p<0.05, **p<0.01, ***p<0.001, ****p<0.0001. FIG.9A: NP-specific IgM and IgG2c antibody forming cells (AFC) per spleen, enumerated by ELISPOT. FIG.9B: Salmonella colony forming units (CFU) per spleen. FIG.9C: Number of IFNγ producing CD4 T cells (left) and B cells (right) per spleen determined by flow cytometry after a 4 hour ex vivo stimulation with PMA / Ionomycin / BrefeldinA. FIG.9D: The % of B cell subsets escaping CD19Credeletion was determined by staining for IFNgR expression by flow cytometry. B-WT controls are solid lines while B-KO samples are dashed lines. Symbols are mean + / - SD. FIGs.9E-9G: The same experiment as in FIGs.9A-9D was performed, comparing CD19Cre+ / -T-betflox / floxmice and Cre-negative T-betflox / floxcontrols. Data are pooled from 2 independent experiments, n=5-10 per group per experiment, symbols represent individual mice and bars the mean + / - SD. FIG.9E: NP-specific IgM and IgG2c AFC per spleen enumerated by ELISPOT. FIG.9F: Salmonella colony forming units (CFU) per spleen. FIG.9G: Number of IFNγ-producing CD4 T cells (left) and B cells (right) per spleen determined by flow cytometry after a 4 hour ex vivo stimulation with PMA / Ionomycin / BrefeldinA. FIG.9H: Bead-purified B cells from CD19Cre+ / -T-betflox / flox(KO) or Cre- negative controls (WT) were cultured for 4 days with LPS + / - recombinant IL-12, IFNγ, or an IL-12 blocking antibody as indicated, “-“ indicates the cytokine was neither added nor blocked. Differentiation as a function of division number was determined as described in FIG.3B. Statistical analysis is 2-way ANOVA with Tukey’s multiple comparisons; data shown are mean + / - SD of cells prepared from 3 individual mice. One of two independent experiments with similar results is shown. FIG.9I: Bead-purified B cells from CD19-Cre+ / - T-betflox / floxmice were cultured for 4 days with LPS + / - IL-12 or blocking antibodies to IL-12 or IFNγ, “-“ indicates the cytokine was neither added nor blocked. Differentiation as a function of division number was compared for n=3 cultures; symbols are mean + / - SD, analyzed by 2-way ANOVA with Tukey’s multiple comparisons. One of two independent experiments with similar results is shown. FIGs.10A-10I. B cell expression of IFNγ receptor, but not T-bet, is necessary for maximal PB response during Salmonella infection. FIG.10A: Additional ELISPOT data described in FIG.9A, NP- specific IgG1 and IgG2b antibody forming cells (AFC), and the sum of IgM+IgG1+IgG2b+IgG2c. FIG. 10B: Example gating for IFNγ producing T and B cells (summarized in FIG.9C). For CD4+ T cells, examples are shown from both infected and HK control mice as different gates for CD44+ cells were necessary. FIG.10C: Example upstream gating for intracellular IFNgR stain, CD19+ and / or CD138+ gate represents B cells + PB, which is then separated in to “PB” or CD138- cells, and then “GC” and the remainder are called “non-GC / PB” which represents a majority naïve cells with minority populations of various resting B cells. FIG.10D: Histograms showing selection of Cre-escape cells among PB populations from B-KO mice (filled histograms). FIG.10E: Additional ELISPOT data as described in FIG.9E. FIG. 10F: Histograms showing T-bet expression among cells gated as in panel I with CD19+ and / or CD138+ gate. FIG.10G: Splenocytes from mice treated for 3 days with recombinant IL-12 in vivo (FIG.3C), were stained for T-bet expression in B cells. A population of T-bet+ IRF4- cells was found to be expanded in IL- 12 treated mice. This population was overlayed on all B cells to show their CD38 CD95 staining in relation to CD38lowCD95hiearly GC B cells. FACS plots are representative of n=5 mice per group with 2 experiments. FIG.10H: Proliferation index of in vitro cultured CD19-Cre+ / - T-bet flox B cells from FIG. 9I. FIG.10I: Representative FACS plots of T-bet staining among CD19-Cre+ / - T-bet flox B cells in indicated conditions from FIG.9I. FIGs.11A-11D. IL-12 and IFNγ synergy for inducing proliferation and differentiation at low concentrations, dependent of autocrine cytokine secretion FIGs.11A-11D: Bead-purified B cells from WT, IL12p40 KO, and IFNg KO mice, were cultured for 4 days with LPS + / - recombinant IL-12, IFNγ, or blocking antibodies, as indicated, “-“ indicates the cytokine was neither added nor blocked. FIG.11A: Differentiation as a function of division number was determined as described for FIG.3B. Statistical analysis by 2-way ANOVA with Tukey’s multiple comparisons. Data shown are mean + / - SD; n=4-5 per group pooled from two independent experiments. FIG.11B: The 20 pg / mL IL-12 + 0.5 ng / mL IFNγ conditions from each mouse strain in FIG.11A are plotted together, and compared by 2-way ANOVA with Tukey’s multiple comparisons. FIG.11C: Representative histograms of VPD dilution on gated live singlet B cells. FIG.11D: Summarized proliferation index data, symbols represent cultures from individual mice and bars the mean + / - SD n=4-5 per group pooled from two independent experiments. Statistical analysis shown is two-tailed Students t test. FIGs.12A-12F. IL-12 and IFNγ induce distinct changes in gene expression in cultured B cells. FIGs.12A-12E: B cells from n=3 WT mice were individually bead-purified and cultured with cytokines and / or blocking antibodies for 4 or 24 hours, as indicated. DEG are determined by comparison to the IL-12- block + IFNγ-block condition for the matched time point control. FIG.12A: Bar charts of the numbers of DEG (log2FC 1, FDR <0.05), the expression of which is up or down relative to control. FIG.12B: Venn diagrams of up-DEG between IL-1220 pg / mL only (block IFNγ), IFNγ 0.5 ng / mL only (block IL-12), or IL-1220 pg / mL + IFNγ 0.5 ng / mL conditions relative to control at 4 (left) and 24 (right) hours. FIG.12C: Curated heat map of DEG, clustered by row. Numbers in boxes are the log2FC of the mean of 3 replicates. Asterisk next to numbers indicates significance (FDR<0.05) of differential regulation compared to the control condition. FIG.12D: Venn diagrams comparing IFNγ 0.5 ng / mL only (block IL-12) at 4 and 24 hours (left), or those plus IL-1220 pg / mL + IFNγ 0.5 ng / mL at 24 hours. FIG.12E: X-Y plot comparing DEG at 24 hours of IL-12-block IFNγ 0.5 ng / mL (x-axis) and IL-1220 pg / mL IFNγ 0.5 ng / mL (y-axis) conditions, to reveal the effects of adding IL-12. Text colors indicate significance with FDR<0.05 for IL-12- block+IFNγ, IL-12+IFNγ, or both conditions. FIG.12F: Proposed model of positive feedback loop, summarizing sequencing results. Upper case protein names refer to protein function, lower case gene names refer to RNA sequencing data. “PROTEIN (Gene)” refers to hypothetical regulatory links between transcription factors and target genes based on existing literature. FIGs.13A-13D. Curated list of DEGs induced by IL-12 and IFNγ treatment. FIG.13A: Experimental design; B cells from three mice were individually bead purified and stimulated with LPS and the indicated concentrations of IL-12, IFNγ, and blocking antibodies for 4 or 24 hours, and RNA was isolated for bulk sequencing. All DEG were compared to IL-12 block + IFNγ block condition for their respective time point. FIG.13B: Venn diagrams comparing up (top) and down (bottom) DEG for 4 hour IFNγ 0.5 ng / mL versus 3 ng / mL both with IL-12 block. FIG.13C: Venn diagrams comparing (top) down DEG for 4 versus 24 hour IFNγ 0.5 ng / mL (block IL-12), (middle) those plus 24 hr IL-1220 pg / mL + IFNγ 0.5 ng / mL, (bottom) or all 24 hr groups; IL-1220 pg / mL (block IFNγ), IFNγ 0.5 ng / mL (block IL-12), or IL-12+IFNγ. FIG.13D: Heatmap of curated list of top DEG of interest clustered by gene names. Numbers in boxes indicate logFC mean of 3 samples, * indicates significance (FDR < 0.05) of differential regulation compared to control. FIG.14. IL-12 and IFNγ DEG are enriched for TH1, Treg, and B cell proliferation genes. Gene set enrichment analysis (GSEA) plots illustrating significant upregulation of TH1Treg, and B cell proliferation related genes at 24 hours of IL-12 and IFNγ samples (n = 3) compared with their control conditions. The P value was calculated using rankSumTestWithCorrelation function from the R limma package. FIGs.15A-15I. IL-12 secreted from B cells influences both B and T cell differentiation in vivo, synergizing with IFNγ signals. FIG.15A: Representative FACS plots of B cells [live, singlet, TCRb- CD45R+] FIG.15A and combined data FIG.15B, from NP-CGG-immunized mice treated with PBS or recombinant IL-12, conducted as described in FIG.3C (day 4 time point). Data are pooled from 2 individual experiments with n=5 per group per experiment, analyzed by two-tailed Students t test. FIGs.15C-15G: Determining cell intrinsic role of IL-12R and IL-12p40 expression on T and B cells respectively during an in vivo immune response. Data shown are pooled from 2 independent experiments with n=4-7 per group per experiment, symbols represent individual mice and bars mean + / - SD. FIG.15C: Experimental design: CD4+ T cells and B cells were bead-purified by depletion of unwanted cells and recombined into 4 cell combinations that were then injected into OTII+ Rag2KO hosts on day -1. Hosts were injected with HK Salmonella, then 2-3 hours later, immunized with NP-CGG at day 0. Splenic PB, AFC, and T cells were assessed 4 days later. FIG.15D: Frequency of PB determined by FACS, and FIG.15E: AFC quantified by ELISPOT. FIG.15F: Frequency of indicated T cell populations as determined by FACS; and FIG.15G: representative FACS plots. FIG.15H: Experimental rationale for design of mixed bone marrow chimeras in FIG.15I, with the null hypothesis being no synergy. FIG.15I: Bone marrow chimeras were reconstituted with 50% / 50% mixtures of bone marrow from CD45.1 WT and one of three KO genotypes carrying the CD45.2 marker: IFNgR1 KO, IL12Rb2 KO, or IFNgR1 KO and IL12Rb2 KO (double KO). After reconstitution, mice were injected with HK or Inf Salmonella on day -3, then NP-CGG on day 0, and spleen cells analyzed 12 days later. Fold-advantage was calculated as described for FIG.3, comparing the population of interest to resting B cells from the same mouse (as in FIG.4), with values above 1 indicating WT advantage. Data combined from 2 HK experiments (HK: n=12 for IL-12R, n=13 for IFNgR and IL- 12R+IFNgR) and 2 Inf experiments (Inf: n=15 IL-12R, n=16 IFNgR, n=14 IL-12R+IFNgR), symbols represent individual mice and bars the mean + / - SD. Individual groups are also tested against the hypothesis of no competitive advantage by one sample t-test (two-tailed) compared to a hypothetical value of 1,(*)p<0.0332,(**)p<0.0021,(***)<0.0002,(****)p<0.0001, and groups compared to each other by two-tailed t-tests. All comparisons in FIGs.15D-15F, 15I, are one-way ANOVA with Tukey’s multiple comparisons, for all chart comparisons are one-tailed Students t test. NS = not significant, *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001. FIGs 16A-16K. In vivo B cell derived IL-12 influences both B and T cells, and synergizes with IFNγ signals for maximal PB differentiation. FIG.16A: Representative FACS plots of spleens of mice treated with PBS or recombinant IL-12 as in FIG.2B, then stimulated 4 hours ex vivo with PMA / Ionomycin and stained for FACS analysis, and FIG.16B: summary data of B cells expressing T-bet and producing IFNγ after IL-12 treatment. Two-tailed Students t test. FIGs.16C-16I: Additional data related to experiment described in FIG.15C. FIG.16C: Gating scheme used to identify donor derived B cells and PB for FIG. 15D. Example shown is from the group IL12RKO T cells + WT B cells. FIG.16D: Example FACS plots of only donor derived B cells (TCRb-, CD19+ or CD138+ from either CD45.1 WT or CD45.2 KO gate), donor genotype is indicated above each chart. FIG.16E: Additional summary from FIG.15D showing the number of CD138+ donor B cells per spleen, and the fold change of IRF4 MFI on PB compared to “naïve” (CD138- CD19+) B cells of the same mouse. FIG.16F: Gating scheme used to analyze CD4 T cells from donor cells, example mouse received WT T cells and WT B cells. FIGs.16G-H: Representative FACS plots of donor derived T cells, genotype indicated above each plot, showing expression of T-bet+ IFNγ+ Th1 cells in FIG. 16G, and CXCR5highBcl6highTFHin FIGs.16H-16I. Example FACS plots (FIG.16H), and summary data (FIG.16I), of the percentage of TFH among donor T cells per mouse. FIG.16J, Additional analysis of mixed bone marrow chimera mice described in FIG.15. Fold advantage was calculated for GC B cells compared to resting cells from the same mouse as described in FIG.4. One-way ANOVA with Tukey’s multiple comparisons was used to compare groups (NS = not significant), and each group was also tested against the hypothesis of no competitive difference by one sample t test compared to a hypothetical value of 1 shown in ( ) above each group, (NS) = not significant,(*)p<0.0332. FIG.16K: Visual representation of the proposed model. Early (4 hours) IL-12 initiates IFNγ production and autocrine IFNγ signals induce expression of genes that both establish negative feedback of IFNγ signaling, and an overlapping positive feedback loop between IL-12 and IFNγ signaling. IFNγ promotes IL-12 signaling by upregulating IL-12 signaling components (IL-12R and STAT4) and STAT1 which IFNγ signals through. At 24 hours, if both IL-12 and IFNγ are present, positive feedback overcomes negative regulation to sustain IFNγ signaling. Additionally, IL-12 and IFNγ synergize to induce genes which are not expressed under either condition alone. FIG.17. Antibodies used in this study. This table provides the list of antibodies, dead cell discriminators and proliferation dye for flow cytometry used in this study, the source, and the dilution or concentration used. FIGs.18A-18F. IL-12 and IFNγ promote proliferation and differentiation of human B cells. Primary human B cells from n=7 individual organ donors were cultured for 8 days with CpG + / - cytokines or blocking antibodies as indicated. FIG.18A: Flow cytometry plots demonstrate upstream gating for one donor example. FIG.18B: Flow cytometry plots show representative analysis from one donor, previously gated on live singlet B cells. Cytokine additions are indicated above each plot. Gates used for quantitation in top panel of FIG.18C are shown. FIG.18C: Summary data of CD38hiIRF4hiPB (top) and frequency of cells that had divided more than once (bottom). Dots and lines connect individual donors, data are combined from 2 individual experiments (n=3 or n=4 donors each experiment, n=7 total). Statistical analysis by one- tailed paired t-tests. FIG.18D: Histograms comparing proliferation of treatment groups for each individual donor. FIGs.18E-18F: Analysis of %PB (CD38hiIRF4hi) per division for each individual donor (n=1 each). Statistical comparisons are multiple paired one-tailed t-tests each compared to block / block. For all charts, NS = not significant, *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001. FIGs.19A-19C. IL-12 and IFNγ production during in vitro B cell stimulation or Salmonella infection of mice. FIGs.19A-19B: B cells from n=3 WT mice were individually purified and cultured with cytokines and / or blocking antibodies for 24 hours, 3 days, or 4 days, as indicated. FIG.19A: Quantification of IL-12 and IFNγ from 24 hour B cell culture supernatants. Data are combined from 2 experiments with n=6 biological replicates per condition represented by symbols, and means represented by bars + / - SD. Comparisons are two-tailed paired t-tests. FIG.19B: Quantification of IL-12 and IFNγ in B cell culture supernatants from 3 time points. Data are combined from 2 experiments, n=6 biological replicates per condition. Symbols represent the mean + / - SD. Comparisons are one-way ANOVA with Tukey’s multiple comparisons for suboptimal cytokine concentrations, and two-tailed paired t-test comparing LPS only to either IL-12 or IFNγ at sufficient concentrations (200 pg / mL and 10 ng / mL respectively), NS = not significant, *p<0.05. FIG.19C: Quantification of IL-12 and IFNγ from sera of mice given Heat Killed (HK) or Infectious (Inf) Salmonella enterica serovar Typhimurium for 3 or 7 days. Data combined from 2 experiments, n=6 per group. FIGs.20A-20B. IL-12 signaling promotes disease progression in a lupus prone mouse model. FIG. 20A: Measurement of protein in the urine (proteinuria) and skin disease on wild type (WT, n=18) and IL- 12Rb2 knock out (KO, n=23) MRL / lpr lupus prone mice at 18 weeks of age. Proteinuria score represents protein concentration in the urine (range 0-4), skin disease is based on size of affected area (range 0-6), statistical comparison is Unpaired two-tailed t test. FIG.20B: Survival analysis of wild type (WT) and IL- 12Rb2 KO (KO) MRL / lpr females, n=11 per group, comparison is Log-rank (Mantel-Cox) test. FIG.21. Cell intrinsic requirements for IL-12 and IFNγ signaling differ between B and CD4+ T cells. Bone marrow chimeras were reconstituted with 50% / 50% mixtures of CD45.1 WT and one of three KO genotypes carrying the CD45.2 marker: IFNgR1 KO, IL12Rb2 KO, or IFNgR1 KO and IL12Rb2 KO (double KO). After reconstitution, mice were injected with Heat Killed (HK) or Infectious (Inf) Salmonella enterica serovar Typhimurium on day -3, NP-CGG on day 0, and spleen cells analyzed 12 days later. Shown are the %plasmablasts (PB, CD138+) and Th1 (IFNγ+ Tbet+ CD4+) T cells among each donor cell type. Note that B cells require both IL-12-receptor (12R) and IFNγ-receptor (IFNgR) to form PB whereas CD4 T cells primarily require IL-12-receptor to form Th1 cells. Shown is one experiment, n=7-8 per group, statistical tests are paired t tests (*<0.05, **p<0.01, ****p<0.0001), and number-x above each comparison is the fold reduction of the mean of each group comparing KO to WT. FIGs.22A-22B. IL-12 / IFNγ dependent expression of CXCR3 and CD326 on B cells. FIG.22A: Mouse bone marrow chimeras were reconstituted with 50% / 50% mixtures of CD45.1 WT and one of three KO genotypes carrying the CD45.2 marker: IFNgR1 KO, IL12Rb2 KO, or IFNgR1 KO and IL12Rb2 KO (double KO). After reconstitution, mice were injected with Infectious Salmonella enterica serovar Typhimurium on day -3, NP-CGG on day 0, and spleen cells analyzed 12 days later. Shown are representative FACS plots of CXCR3 expression on KO cells compared to WT cell controls, n=7-8 per group, one experiment of two is shown. FIG.22B: Primary human B cells from n=4 individual organ donors were cultured for 8 days with CpG + / - cytokines or blocking antibodies as indicated. Shown is a representative histogram overlay of samples from the same donor treated with the indicated cytokines (top), and summary data from 4 donors. Statistical comparisons are all Paired t tests (*p<0.05, **p<0.01). DETAILED DESCRIPTION I. Introduction It is disclosed herein that IL-12 antagonists are of use for the treatment of specific subsets of subjects with autoimmune diseases. In some aspects, methods are disclosed for selecting a subject that can be treated with an IL-12 antagonist. These methods include detecting i) an increase in DN1 cells, DN2 cells, DN3 cells, and / or plasmablasts in a biological sample obtained from the subject as compared a control, ii) an increase of T-bet, CXCR3, CD326, VISTA, Ly6H, CD317 and / or IFNγ expressing lymphocytes in a biological sample obtained from the subject as compared to a control; iii) elevated serum concentration of IL-12 and / or IFNγ as compared to a control, and / or iv) elevated anti-RNA or anti-Smith (SM) antibodies in a biological sample obtained from the subject as compared to a control. Subjects with one or more of these parameters are amenable to treatment with an IL-12 antagonist. In some aspects, methods are disclosed for treating a subject with an autoimmune disease that include selecting a subject with the autoimmune disease that has i) an increase in DN1 cells, DN2 cells, DN3 cells, and / or plasmablasts in a biological sample obtained from the subject as compared a control, ii) an increased in T-bet, CXCR3, CD326, VISTA, Ly6H, CD317 and / or IFNγ expressing lymphocytes in a biological sample obtained from the subject as compared to a control; iii) elevated serum concentration of IL-12 and / or IFNγ as compared to a control, and / or iv) elevated anti-RNA or anti-Smith (SM) antibodies in a biological sample obtained from the subject as compared to a control. The methods also include administering to the subject an effective amount of IL-12 antagonist, thereby treating the autoimmune disease in the subject. II. Abbreviations 3SR self-sustained sequence replication system AAV adeno-associated virus AFC antibody forming cells ALBIA addressable laser bead immunoassays APC antigen presenting cells BCIP / NBT 5-bromo-4-chloro-3-indolyl-phosphate and nitroblue tetrazolium BCL B-cell lymphoma BCR B-cell antigen receptor BILAG British Isles Lupus Assessment Group B-KO B cell specific KO, either CD19Cre+ / -IFNgR1flox / floxB6 or CD19Cre+ / -T-betflox / floxB6 mice BM bone marrow B-WT Cre-negative IFNgR1flox / floxor T-betflox / floxcontrols CD cluster of differentiation CD4 cluster of differentiation 4 CD8 cluster of differentiation 8 CTL cytotoxic T cells CFU colony forming units CLIA chemiluminescent immunoassays Ctl WT control wild-type CXC chemokine receptor DEG differentially expressed genes DMARDS disease-modifying antirheumatic drugs DN double negative dsRNA double stranded RNA DTE dithioerythritol EF extrafollicular ELISA enzyme-linked immunosorbent assays EM effector molecule EpCAM epithelial adhesion molecule ESI-MS electrospray ionization mass spectrometry FACS fluorescence activated cell sorting FDA US Food and Drug Administration FEIA fluorescent enzyme immunoassays GC germinal center GC / MS gas chromatography / mass spectrometry GPI glycosyl-phosphatidylinositol GPR9 G protein-coupled receptor 9 GSEA gene-set enrichment analysis GSSG oxidized glutathione HCDR heavy chain complementarity determining regions HK Ctl heat killed control IBD inflammatory bowel disease IFN interferon IFNgR1 interferon gamma receptor 1 IFNgR2 interferon gamma receptor 2 IG immunoglobins IIFT indirect immunofluorescence tests IL interleukin IRF Interferon regulatory factor IVIGs intravenous immunoglobulins KO knock-out LAK lymphokine activated killer LCDR light chain complementarity regions LCR ligase chain reaction LGL large granular lymphocytes LIA line immunoassays Ly6H lymphocyte antigen 6 family member H mRNA messenger RNA MALDI-TOF matrix-assisted laser desorption / ionization-time of flight MS mass spectrometry MS / MS tandem mass spectrometry NK natural killer NKSF natural killer stimulating factor NP 4-hydroxy-5-iodo-3-nitrophenyl NP-CGG nitrophenyl-Chicken Gamma Globulin NP-specific NIP+CD19+B cells; B cells that bind the antigen NIP NS not significant NSAIDS nonsteroidal anti-inflammatory drugs PB plasmablasts PCR polymerase chain reaction PD-1 programmed death 1 PG Physician's Global Assessment of Disease Activity RBC red blood cells RIA radioactive immunoassay RNAi interference RNA scFv single-chain antigen binding proteins SDR specificity determining residue database SLEDAI Systemic Lupus Erythematosus Disease Activity Index siRNA small inhibitory RNA SLE systemic lupus erythematosus SM Smith snRNA small nuclear RNA snRNP small nuclear ribonucleoprotein Stm Salmonella enterica serovar Typhimurium SV40 simian virus 40 T-APC antigen presenting T-cell TAS transcription-based amplification system Tc cells cytotoxic T lymphocytes TCR T-cell antigen receptors Th helper T cells TLR toll like receptor TMS Trimethroprim sulfadiazine UCTD undifferentiated connective tissue disease VISTA V-domain Ig suppressor of T cell activation VPD Violet proliferation dye WT wild-type III. Summary of Terms Unless otherwise noted, technical terms are used according to conventional usage. Definitions of many common terms in molecular biology may be found in Krebs et al. (eds.), Lewin’s genes XII, published by Jones & Bartlett Learning, 2017. As used herein, the singular forms “a,” “an,” and “the,” refer to both the singular as well as plural, unless the context clearly indicates otherwise. For example, the term “an antigen” includes singular or plural antigens and can be considered equivalent to the phrase “at least one antigen.” As used herein, the term “comprises” means “includes.” “It is further to be understood that any and all base sizes or amino acid sizes, and all molecular weight or molecular mass values, given for nucleic acids or polypeptides are approximate, and are provided for descriptive purposes, unless otherwise indicated. Although many methods and materials similar or equivalent to those described herein can be used, particular suitable methods and materials are described herein. In case of conflict, the present specification, including explanations of terms, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting. To facilitate review of the various aspects, the following explanations of terms are provided: About: Unless context indicates otherwise, “about” refers to plus or minus 5% of a reference value. For example, “about” 100 refers to 95 to 105. Antagonist: An agent that binds to a receptor or an enzyme and inhibits an action, such as a biologic activity. For example, an antagonist that binds to a cellular receptor inhibits a physiological or pharmacological response that would occur when the ligand binds the cellular receptor. An IL-12 antagonist inhibits an activity of IL-12. Antibody and Antigen Binding Fragment: An immunoglobulin, antigen-binding fragment, or derivative thereof, that specifically binds and recognizes an analyte (antigen) such as IL-12. The term “antibody” is used herein in the broadest sense and encompasses various antibody structures, including but not limited to monoclonal antibodies, polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies), and antigen binding fragments, so long as they exhibit the desired antigen-binding activity. Non-limiting examples of antibodies include, for example, intact immunoglobulins and variants and fragments thereof that retain binding affinity for the antigen. Examples of antigen binding fragments include but are not limited to Fv, Fab, Fab’, Fab’-SH, F(ab’)2; diabodies; linear antibodies; single-chain antibody molecules (e.g., scFv); and multispecific antibodies formed from antibody fragments. Antibody fragments include antigen binding fragments either produced by the modification of whole antibodies or those synthesized de novo using recombinant DNA methodologies (see, e.g., Kontermann and Dübel (Eds.), Antibody Engineering, Vols.1-2, 2nded., Springer-Verlag, 2010). Antibodies also include genetically engineered forms such as chimeric antibodies (such as humanized murine antibodies) and heteroconjugate antibodies (such as bispecific antibodies). An antibody may have one or more binding sites. If there is more than one binding site, the binding sites may be identical to one another or may be different. For instance, a naturally-occurring immunoglobulin has two identical binding sites, a single-chain antibody or Fab fragment has one binding site, while a bispecific antibody has two different binding sites. Typically, a naturally occurring immunoglobulin has heavy (H) chains and light (L) chains interconnected by disulfide bonds. Immunoglobulin genes include the kappa, lambda, alpha, gamma, delta, epsilon and mu constant region genes, as well as the myriad immunoglobulin variable domain genes. There are two types of light chain, lambda (λ) and kappa (κ). There are five main heavy chain classes (or isotypes) which determine the functional activity of an antibody molecule: IgM, IgD, IgG, IgA and IgE. Each heavy and light chain contains a constant region (or constant domain) and a variable region (or variable domain). In combination, the heavy and the light chain variable regions specifically bind the antigen. References to “VH” or “VH” refer to the variable region of an antibody heavy chain, including that of an antigen binding fragment, such as Fv, scFv, dsFv or Fab. References to “VL” or “VL” refer to the variable domain of an antibody light chain, including that of an Fv, scFv, dsFv or Fab. The VH and VL contain a “framework” region interrupted by three hypervariable regions, also called “complementarity-determining regions” or “CDRs” (see, e.g., Kabat et al., Sequences of Proteins of Immunological Interest, 5thed., NIH Publication No.91-3242, Public Health Service, National Institutes of Health, U.S. Department of Health and Human Services, 1991). The sequences of the framework regions of different light or heavy chains are relatively conserved within a species. The framework region of an antibody, that is the combined framework regions of the constituent light and heavy chains, serves to position and align the CDRs in three-dimensional space. The CDRs are primarily responsible for binding to an epitope of an antigen. The amino acid sequence boundaries of a given CDR can be readily determined using any of a number of well-known schemes, including those described by Kabat et al. (Sequences of Proteins of Immunological Interest, 5thed., NIH Publication No.91-3242, Public Health Service, National Institutes of Health, U.S. Department of Health and Human Services, 1991; “Kabat” numbering scheme), Al-Lazikani et al., (“Standard conformations for the canonical structures of immunoglobulins,” J. Mol. Bio., 273(4):927-948, 1997; “Chothia” numbering scheme), and Lefranc et al. (“IMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domains,” Dev. Comp. Immunol., 27(1):55-77, 2003; “IMGT” numbering scheme). The CDRs of each chain are typically referred to as CDR1, CDR2, and CDR3 (from the N-terminus to C-terminus), and are also typically identified by the chain in which the particular CDR is located. Thus, a VHCDR3 is the CDR3 from the VHof the antibody in which it is found, whereas a VLCDR1 is the CDR1 from the VLof the antibody in which it is found. Light chain CDRs are sometimes referred to as LCDR1, LCDR2, and LCDR3. Heavy chain CDRs are sometimes referred to as HCDR1, HCDR2, and HCDR3. In some aspects, an antibody of use in the disclosed methods includes a heterologous constant domain. For example, the antibody includes a constant domain that is different from a native constant domain, such as a constant domain including one or more modifications (such as the “LS” mutations) to increase half-life. A “monoclonal antibody” is an antibody obtained from a population of substantially homogeneous antibodies, that is, the individual antibodies comprising the population are identical and / or bind the same epitope, except for possible variant antibodies, for example, containing naturally occurring mutations or arising during production of a monoclonal antibody preparation, such variants generally being present in minor amounts. In contrast to polyclonal antibody preparations, which typically include different antibodies directed against different determinants (epitopes), each monoclonal antibody of a monoclonal antibody preparation is directed against a single determinant on an antigen. Thus, the modifier “monoclonal” indicates the character of the antibody as being obtained from a substantially homogeneous population of antibodies, and is not to be construed as requiring production of the antibody by any particular method. For example, the monoclonal antibodies may be made by a variety of techniques, including but not limited to the hybridoma method, recombinant DNA methods, phage-display methods, and methods utilizing transgenic animals containing all or part of the human immunoglobulin loci, such methods and other exemplary methods for making monoclonal antibodies being described herein. In some examples monoclonal antibodies are isolated from a subject. Monoclonal antibodies can have conservative amino acid substitutions which have substantially no effect on antigen binding or other immunoglobulin functions. (See, for example, Greenfield (Ed.), Antibodies: A Laboratory Manual, 2nded. New York: Cold Spring Harbor Laboratory Press, 2014.) A “humanized” antibody or antigen binding fragment includes a human framework region and one or more CDRs from a non-human (such as a mouse, rat, or synthetic) antibody or antigen binding fragment. The non-human antibody or antigen binding fragment providing the CDRs is termed a “donor,” and the human antibody or antigen binding fragment providing the framework is termed an “acceptor.” In one aspect, all the CDRs are from the donor immunoglobulin in a humanized immunoglobulin. Constant regions need not be present, but if they are, they can be substantially identical to human immunoglobulin constant regions, such as at least about 85-90%, such as about 95% or more identical. Hence, all parts of a humanized antibody or antigen binding fragment, except possibly the CDRs, are substantially identical to corresponding parts of natural human antibody sequences. A “chimeric antibody” is an antibody which includes sequences derived from two different antibodies, which typically are of different species. In some examples, a chimeric antibody includes one or more CDRs and / or framework regions from one human antibody and CDRs and / or framework regions from another human antibody. A “fully human antibody” or “human antibody” is an antibody which includes sequences from (or derived from) the human genome and does not include sequence from another species. In some aspects, a human antibody includes CDRs, framework regions, and (if present) an Fc region from (or derived from) the human genome. Human antibodies can be identified and isolated using technologies for creating antibodies based on sequences derived from the human genome, for example by phage display or using transgenic animals (see, e.g., Barbas et al. Phage display: A Laboratory Manuel. 1stEd. New York: Cold Spring Harbor Laboratory Press, 2004. Print.; Lonberg, Nat. Biotech., 23: 1117-1125, 2005; Lonenberg, Curr. Opin. Immunol., 20:450-459, 2008). Antigen-presenting cell (APC): A cell that can present antigen bound to MHC class I or class II molcules to T cells. APCs include, but are not limited to, monocytes, macrophages, dendritic cells, B cells, T cells and Langerhans cells. A T cell that can present antigen to other T cells (including CD4+ and / or CD8+ T cells) is an antigen presenting T cell (T-APC). Autoimmune Disease: A disease in which the immune system produces an immune response (for example, a B-cell or a T-cell response) against an antigen that is part of the normal host (that is, an autoantigen), with consequent injury to tissues. Exemplary autoimmune diseases affecting mammals include rheumatoid arthritis, juvenile oligoarthritis, collagen-induced arthritis, adjuvant-induced arthritis, Sjogren’s syndrome, multiple sclerosis, experimental autoimmune encephalomyelitis, inflammatory bowel disease (for example, Crohn’s disease, ulcerative colitis), autoimmune gastric atrophy, pemphigus vulgaris, psoriasis, vitiligo, type 1 diabetes, non-obese diabetes, myasthenia gravis, Grave’s disease, Hashimoto’s thyroiditis, sclerosing cholangitis, sclerosing sialadenitis, systemic lupus erythematosus, autoimmune thrombocytopenia purpura, Goodpasture’s syndrome, Addison’s disease, systemic sclerosis, polymyositis, dermatomyositis, autoimmune hemolytic anemia, pernicious anemia, and the like. Autoimmune diseases include systemic autoimmune diseases, which affect more than one organ, and a tissue specific organ disease, which affects only one organ. Autoimmune diseases include rheumatic diseases. B Cell: A lymphocyte, a type of white blood cell (leukocyte), that develops into a plasma cell (a “mature B cell”), which produces antibodies. An “immature B cell” is a cell that can develop into a mature B cell. Generally, pro-B cells (that express, for example, CD45 or B220 (CD45R, mouse)) undergo immunoglobulin heavy chain rearrangement to become pro B pre B cells, and further undergo immunoglobulin light chain rearrangement to become immature B cells. Immature B cells include T1 and T2 B cells. Thus, one example of an immature B cell is a T1 B that is an AA41hiCD23locell. Another example of an immature B cell is a T2 B that is an AA41hiCD23hicell. Immature B cells include B220 expressing cells wherein the light and the heavy chain immunoglobulin genes are rearranged, and that express AA41. Immature B cells can develop into mature B cells, which can produce immunoglobulins (e.g., IgA, IgG or IgM). Mature B cells express characteristic markers such as CD21 and CD23 (CD23hiCD21hicells), but do not express AA41. B cells can be activated by agents such as lipopolysaccharide (LPS) or IL-4 and antibodies to IgM. The marker CD19 is specific to the B cell lineage. Double negative (DN) B cells, also called age associated B cells (ABC) cells, are memory B cells that produce antibodies that play a role in the regulation of the humoral response. DN B cells express CD19, but do not express IgD or CD27, and thus are CD19+CD27-IgD- (see Jenks et al., Immunity 49(4): 725-736, 2018). There are several subpopulations of DN B cells. DN1 B cells are CD19+ CD27- IgD- CD11c(+ or - )CXCR5+ (see Jenks et al., Immunity 49(4): 725-736, 2018). DN2 B cells are CD19+ CD27- IgD- CD11c+ CXCR5-. DN3 B cells are CD19+ CD27- IgD- CD11c- CXCR5- (see Chamard et al., Cell Reports 42: 12630, June 27, 2023). B-cell lymphoma (Bcl): A master transcription factor for regulation of T follicular helper cells (TFHcells) differentiation. Bcl6 has three evolutionary conserved structural domains. The interaction of these domains with corepressors allows for germinal center development and leads to germinal center B cell formation. The deletion of BCL6 leads to failure of germinal center formation in the follicles of the lymph nodes, preventing B cells from undergoing somatic hypermutation. An exemplary amino acid sequence for human Bcl6, and a nucleic acid sequence encoding Bcl6, are provided in GENBANK® Accession No. NG_007149.1, September 26, 2021. Biological sample: A sample obtained from a subject. Biological samples include all clinical samples useful for detection of disease or infection (for example, an autoimmune disease) in subjects, including, but not limited to, cells, tissues, and bodily fluids, such as blood, derivatives and fractions of blood (such as serum), cerebrospinal fluid; as well as biopsied or surgically removed tissue, for example tissues that are unfixed, frozen, or fixed in formalin or paraffin. Cluster of Differentiation (CD): This is a nomenclature system for antigens found on lymphocytes, although CD antigens can be found on cells other than lymphocytes. Cluster of differentiation is nomenclature used to name antigens recognized by monoclonal antibodies that specifically bind an antigen on cells. Each numeric antigen is a specific protein that is recognized in the art by its CD designation. CD3: A specific protein complex including at least four polypeptide chains, which are non- covalently associated with the T cell receptors on the surface of T cells. The four polypeptide chains include two CD3-epsilon chains, a CD3-delta chain and a CD3-gamma chain. CD3 is present on both helper T cells and cytotoxic T cells. CD11c: A type I transmembrane protein, encoded by the gene Itgax, that is expressed on monocytes, granulocytes, a subset of B cells, dendritic cells. CD11c is abundantly expressed in monocytes and macrophages. An exemplary amino acid sequence of human CD11c, and an exemplary nucleic acid sequence encoding CD11c, is disclosed in GENBANK Accession No. NG_011451, May 13, 2020, incorporated herein by reference. CD19: An antigen also known as B4, Leu12, CVID3 or MGC12802, which is expressed on B cells. An exemplary nucleic acid sequence and amino acid sequence of CD19 is provided in GENBANK® Accession No. NG_007275 (human), June 26, 2023, which is incorporated by reference herein. CD20: An antigen also called human B-lymphocyte-restricted differentiation antigen or Bp35 that is a hydrophobic transmembrane protein with a molecular weight of approximately 35 kD located on pre-B and mature B lymphocytes (Valentine et al., J. Biol. Chem.264(19):11282-11287, 1989; and Einfield et al., EMBO J.7(3):711-717, 1988). In vivo, CD20 is found on the surface of greater than 90% of B cells from peripheral blood or lymphoid organs and is expressed during early pre-B cell development and remains expressed until plasma cell differentiation. CD20 is present on both normal B cells and malignant B cells, but is not found on hematopoietic stem cells, pro-B cells, normal plasma cells, or other normal tissues (Tedder et al., J. Immunol.135(2):973-979, 1985). CD20 is involved in regulating early steps in the activation and differentiation process of B cells (Tedder et al., Eur. J. Immunol.16:881-887, 1986) and can function as a calcium ion channel (Tedder et al., J. Cell. Biochem.14D:195, 1990). Exemplary amino acid sequences for CD20 are provided in GENBANK® Accession Nos. NP_068769.2 (human), NP_690605.1 (human), and NP_031667.1 (mouse), as available on July 1, 2023, incorporated herein by reference. See also GENBANK® Accession No. NG_0122861.1, July 9, 2020, incorporated herein by reference, for an exemplary amino acid and exemplary nucleic acid sequences of human CD20). CD27: A member of the tumor necrosis factor receptor superfamily that binds to the ligand CD70 and plays a role in regulating B cell activation and immunoglobulin synthesis. When CD27 binds CD70, a signaling cascade leads to the differentiation and clonal expansion of T cells. This cascade also results in improved survival and memory of cytotoxic T cells and increased production of certain cytokines. An exemplary amino acid sequence of CD27, and an exemplary nucleotide sequence encoding this protein, are provided in GENBANK Accession No. NG_031995.1, June 1, 2023, incorporated herein by reference. CD38: A glycoprotein, also known as ADP ribose hydrolase, found on the surface of plasma B cells, natural killer cells, and T cells, including CD4+ T cell, CD8+ T cell, B lymphocytes and natural killer cells. CD38 also functions in cell adhesion, signal transduction and calcium signaling. CD38 is a multifunctional enzyme that catalyzes the synthesis of ADP ribose and cyclic ADP-ribose (3%) from NAD+. An exemplary amino acid sequence of CD38 is provided in GENBANK Accession No. NP_001766, May 29, 2023, incorporated herein by reference. CD138: A protein also known as syndecan-1, that is a transmembrane (type I) heparan sulfate proteoglycan and is a member of the syndecan proteoglycan family. CD138 functions as an integral membrane protein and participates in cell proliferation, cell migration and cell-matrix interactions via its receptor for extracellular matrix proteins. An exemplary amino acid sequence of CD138, and a nucleotide sequence encoding this protein, are provided in GENBANK Accession No. NG_050639.2, September 14, 2022, incorporated herein by reference. CD317: A lipid raft associated protein that is known as tetherin or bone marrow stromal antigen 2. CD317 is constitutively expressed in mature B cells, plasma cells and plasmacytoid dendritic cells. It can be expressed as a response to stimulation from the IFN pathway. CD317 is an integral membrane protein, with the N-terminus in the cytoplasm, one membrane spanning domain, and a C-terminus modified by the addition of a glycosyl-phosphatidylinositol (GPI) anchor. CC317+ B cells are a marker for clinical flares in SLE (see El-Sherbiny et al., Arthritis and Rheumatology 72(5): 769-779 (May 2020)). An exemplary nucleic acid sequence and amino acid sequence of CD317 is provided in GENBANK® Accession No. NM_004335.4 (human), June 26, 2023, which is incorporated by reference herein. CD326: A protein also known as epithelial adhesion molecule (EpCAM), that is a transmembrane glycoprotein mediating Ca2+-independent homotypic cell–cell adhesion in epithelia CD326 is also involved in cell signaling, migration, proliferation, and differentiation. CD326 is a marker of human plasma cells and identifies a bone marrow specific subpopulation in patients with SLE (see Dang et al., Front. Immunology, Sec. B, Biology 13, doi.org / 10.3389 / fimmu.2022.873217 (April 8, 2022). An exemplary nucleic acid sequence and amino acid sequence of CD317 is provided in GENBANK® Accession No. NG_012352 (human), June 26, 2023, which is incorporated by reference herein. Conditions sufficient to form an immune complex: Conditions that allow an antibody or antigen binding fragment to bind to its cognate epitope to a detectably greater degree than, and / or to the substantial exclusion of, all other epitopes, and thus be detected. Conditions sufficient to form an immune complex are dependent upon the format of the binding reaction and typically are those utilized in immunoassay protocols, or those conditions encountered in vivo. See Harlow & Lane, Antibodies, A Laboratory Manual, 2nded. Cold Spring Harbor Publications, New York (2013) for a description of immunoassay formats and conditions. The conditions employed in the methods are “physiological conditions” which include reference to conditions (e.g., temperature, osmolarity, pH) that are typical inside a living mammal or a mammalian cell. While it is recognized that some organs are subject to extreme conditions, the intra-organismal and intracellular environment normally lies around pH 7 (e.g., from pH 6.0 to pH 8.0, more typically pH 6.5 to 7.5), contains water as the predominant solvent, and exists at a temperature above 0°C and below 50°C. Osmolarity is within the range that is supportive of cell viability and proliferation. Control: A reference standard. In some examples, the control is a negative control sample obtained from a healthy subject (e.g., one not having an autoimmune disease). In other examples, the control is a positive control sample obtained from a subject diagnosed with the autoimmune disease. In still other examples, the control is a historical control or standard reference value or range of values (such as a previously tested control sample, such as a group of subjects with known prognosis or outcome, or group of samples that represent baseline or normal values from subjects that do not have an autoimmune disease). A practitioner can readily determine an appropriate control. A difference between a test sample and a control can be an increase or conversely a decrease. The difference can be a qualitative difference or a quantitative difference, for example a statistically significant difference. In some examples, a difference is an increase or decrease, relative to a control, of at least about 5%, such as at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 100%, at least about 150%, at least about 200%, at least about 250%, at least about 300%, at least about 350%, at least about 400%, at least about 500%, or greater than 500%. CXC Chemokine Receptor (CXCR)3: A Gαiprotein-coupled receptor in the CXC chemokine receptor family. Other names for CXCR3 are G protein-coupled receptor 9 (GPR9) and CD183. An exemplary amino acid, and nucleic acid sequence encoding, CXCR3 are provided in GENBANK Accession No. NG_029076, incorporated herein by reference. CXCR5: A G-protein coupled seven transmembrane receptor, also known as Burkitt lymphoma receptor 1, that is the receptor for chemokine CXCL13, also known as BLC. This receptor plays a role in B cell migration. CXCR5 is also known as CD185. Exemplary amino acid sequences and nucleic acid sequences for CXCR5 are disclosed in GENBANK® Accession No. NM_001716.5, May 23, 2023, GENBANK® Accession No. NM_032966.2, May 23, 2023, and GENBANK® Accession No. XM_054369641, March 20, 2023, all incorporated by reference herein. Contacting or contact: A spatial relationship between two items, such as an antigen and an antibody, provided for a time and under condition such that a reciprocal or non-reciprocal action or influence between the two items can be exerted. Detectable marker: A detectable molecule (also known as a label) that is conjugated directly or indirectly to a second molecule, such as a humanized monoclonal antibody, to facilitate detection of the second molecule. For example, the detectable marker can be capable of detection by ELISA, spectrophotometry, flow cytometry, microscopy or diagnostic imaging techniques (such as CT scans, MRIs, ultrasound, fiberoptic examination, and laparoscopic examination). Specific, non-limiting examples of detectable markers include fluorophores, chemiluminescent agents, enzymatic linkages, radioactive isotopes and heavy metals or compounds (for example super paramagnetic iron oxide nanocrystals for detection by MRI). Methods for using detectable markers and guidance in the choice of detectable markers appropriate for various purposes are discussed for example in Green and Sambrook (Molecular Cloning: A Laboratory Manual, 4thed., New York: Cold Spring Harbor Laboratory Press, 2012) and Ausubel et al. (Eds.) (Current Protocols in Molecular Biology, New York: John Wiley and Sons, including supplements, 2017). Detecting: To identify the existence, presence, or fact of something. Effective amount: A quantity of a specific substance sufficient to achieve a desired effect in a subject to whom the substance is administered, such as a therapeutically effective amount, for treatment. For instance, this can be the amount of an IL-12 antagonist necessary to inhibit an autoimmune response or to measurably alter outward symptoms of an autoimmune disease. In some aspects, administration of an effective amount of an IL-12 antagonist can reduce or inhibit an autoimmune response, or a symptom of an autoimmune disease by a desired amount, for example by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98%, or even at least 100% (elimination of the tumor), as compared to a suitable control, such as in a subject not administered the IL-12 antagonist. The effective amount of an IL-12 antagonist that is administered to a subject may vary depending on a number of factors associated with that subject, for example the overall health and / or weight of the subject. An effective amount can be determined by varying the dosage and measuring the resulting response. Effective amounts also can be determined through various in vitro, in vivo or in situ immunoassays. An effective amount encompasses a fractional dose that contributes in combination with previous or subsequent administrations to attaining an effective response. For example, an effective amount of an agent can be administered in a single dose, or in several doses, for example daily or during a course of treatment lasting several days or weeks. However, the effective amount can depend on the subject being treated, the severity and type of the condition being treated, and the manner of administration. A unit dosage form of the agent can be packaged in an amount, or in multiples of the effective amount, for example, in a vial (e.g., with a pierceable lid) or syringe having sterile components. Fc region: The constant region of an antibody excluding the first heavy chain constant domain. Fc region generally refers to the last two heavy chain constant domains of IgA, IgD, and IgG, and the last three heavy chain constant domains of IgE and IgM. An Fc region may also include part or all of the flexible hinge N-terminal to these domains. For IgA and IgM, an Fc region may or may not include the tailpiece, and may or may not be bound by the J chain. For IgG, the Fc region is typically understood to include immunoglobulin domains Cγ2 and Cγ3 and optionally the lower part of the hinge between Cγ1 and Cγ2. Although the boundaries of the Fc region may vary, the human IgG heavy chain Fc region is usually defined to include residues following C226 or P230 to the Fc carboxyl-terminus, wherein the numbering is according to Kabat. For IgA, the Fc region includes immunoglobulin domains Cα2 and Cα3 and optionally the lower part of the hinge between Cα1 and Cα2. IgD: A monomeric antibody isotype that is expressed in the plasma membrane of B cells and is secreted into the blood stream. IgD specifically is involved in signaling B cell activation. Secreted IgD is made of up two heavy chains of the delta class and two light chains. Exemplary amino acid sequences and nucleic acid sequence for IgD are provided in GENBANK® Accession No. NG_031995, April 23, 2016, which is incorporated by reference herein, and GENBANK Accession No. NG_001019.6, May 31, 2023, incorporated by reference herein. Immune complex: The binding of antibody or antigen binding fragment (such as a scFv) to a soluble antigen forms an immune complex. The formation of an immune complex can be detected through conventional methods, for instance immunohistochemistry, immunoprecipitation, flow cytometry, immunofluorescence microscopy, ELISA, immunoblotting (for example, Western blot), magnetic resonance imaging, CT scans, radiography, and affinity chromatography. Immune response: A response of a cell of the immune system, such as a B cell, or a T cell, to a stimulus. A “parameter of an immune response” is any particular measurable aspect of an immune response, including, but not limited to, cytokine secretion, immunoglobulin production, dendritic cell maturation, and proliferation of a cell of the immune system. One of skill in the art can readily determine an increase in any one of these parameters, using known laboratory assays. In one specific non-limiting example, to assess cell proliferation, incorporation of3H-thymidine can be assessed. A “substantial” increase in a parameter of the immune response is a significant increase in this parameter as compared to a control. Specific, non-limiting examples of a substantial increase are at least about a 50% increase, at least about a 75% increase, at least about a 90% increase, at least about a 100% increase, at least about a 200% increase, at least about a 300% increase, and at least about a 500% increase. Similarly, an inhibition or decrease in a parameter of the immune response is a significant decrease in this parameter as compared to a control. Specific, non-limiting examples of a substantial decrease are at least about a 50% decrease, at least about a 75% decrease, at least about a 90% decrease, at least about a 100% decrease, at least about a 200% decrease, at least about a 300% decrease, and at least about a 500% decrease. A statistical test, such as a non-parametric ANOVA, can be used to compare differences in the magnitude of the response induced by one agent as compared to the percent of samples that respond using a second agent. In some examples, p ≤ 0.05 is significant, and indicates a substantial increase or decrease in the parameter of the immune response. One of skill in the art can readily identify other statistical assays of use. Inhibiting a disease or condition: Reducing the full development of a disease or condition in a subject, for example, reducing the full development of an autoimmune in a subject who is at risk of having the autoimmune disease, or reducing a flare-up in a subject with the autoimmune disease. This includes neutralizing, antagonizing, prohibiting, preventing, restraining, slowing, disrupting, stopping, or reversing progression or severity of the disease or condition. Inhibiting a disease or condition can refer to a prophylactic intervention administered before the disease or condition has begun to develop (for example a treatment initiated in a subject at risk of for the autoimmune disease, or prior to a flare-up of the autoimmune disease) that reduces subsequent development of the disease or condition and / or ameliorates a sign or symptom of the disease or condition following development. The term “ameliorating,” with reference to inhibiting a disease or condition refers to any observable beneficial effect of the prophylactic intervention intended to inhibit the disease or condition. The beneficial effect can be evidenced, for example, by a delayed onset of clinical symptoms of the disease or condition in a susceptible subject, a reduction in severity of some or all clinical symptoms of the disease or condition, a slower progression of the disease or condition, an improvement in the overall health or well- being of the subject, a reduction in a immune response, or by other parameters known in the art that are specific to the particular disease or condition. In some aspects, the IL-2 antagonist inhibit an autoimmune disease in a subject. Interleukin (IL)-12: A heterodimeric cytokine consisting of glycosylated polypeptide chains of 35 and 40 kD which are disulfide bonded. IL-12 is synthesized and secreted by antigen presenting cells including dendritic cells, monocytes, macrophages, B cells, Langerhans cells and keratinocytes as well as natural killer (NK) cells. IL-12 mediates a variety of biological processes and has been referred to as NK cell stimulatory factor (NKSF), T-cell stimulating factor, cytotoxic T-lymphocyte maturation factor and EBV-transformed B-cell line factor (Curfs, J. H. A. J., et al., Clinical Microbiology Reviews, 10:742-780 (1997)). IL-12 is encoded by two separate genes, IL-12A (p35) and IL-12B (p40). The active heterodimer (referred to as “IL-12 p70”), and a homodimer of p40 are formed following protein synthesis. An amino acid sequence for IL-12 A, and an mRNA encoding this protein, are available as GENBANK® Accession No. NM_000882.4, May 29, 2023, incorporated herein by reference. An exemplary amino acid sequence for IL-12 A, and an exemplary nucleic acid sequence of mRNA encoding IL-12, are available as GENBANK® Accession No. NM_002187, May 24, 2023, incorporated herein by reference. Interferon (IFN)γ: A dimerized soluble cytokine that is the only member of the type II class of interferons. The IFN-γ monomer consists of a core of six α-helices and an extended unfolded sequence in the C-terminal region; the biologically active dimer is formed by anti-parallel inter-locking of the two monomers. Cellular responses to IFNγ are activated through its interaction with a heterodimeric receptor consisting of Interferon gamma receptor 1 (IFNgR1) and Interferon gamma receptor 2 (IFNgR2). IFNγ plays a role in regulating the immune response of its target cell. IFNγ activates the JAK-STAT signaling pathway. By activating signaling pathways in cells such as macrophages, B cells, and CD8+ cytotoxic T cells, IFNγ can promote inflammation, antiviral activity, antibacterial activity, cell proliferation and differentiation. An exemplary amino acid sequence of human IRF4, and an exemplary nucleotide sequence encoding IFNγ, are disclosed in GENBANK Accession No. NG_015840, January 31, 2022, incorporated herein by reference. Interferon Regulatory Factor (IRF4): A protein in the IRF family of transcription factors, characterized by a unique tryptophan pentad repeat DNA-binding domain. The IRFs are important in the regulation of interferons in response to infection by virus, and in the regulation of interferon-inducible genes. This family member is lymphocyte specific and negatively regulates Toll-like-receptor (TLR) signaling that is central to the activation of innate and adaptive immune systems. An exemplary amino acid sequence of human IRF4, and an exemplary nucleotide sequence encoding IRF4, are disclosed in GENBANK Accession No. NG_027728.1, July 5, 2020, incorporated herein by reference. Isolated: An “isolated” biological component (such as a nucleic acid, peptide, or protein) has been substantially separated, produced apart from, or purified away from other biological components in the cell of the organism in which the component naturally occurs, i.e., other chromosomal and extrachromosomal DNA and RNA, and proteins. Nucleic acids, peptides and proteins which have been “isolated” thus include nucleic acids and proteins purified by standard purification methods. The term also embraces nucleic acids, peptides and proteins prepared by recombinant expression in a host cell as well as chemically synthesized nucleic acids. Similarly, an “isolated” cell has been substantially separated, produced apart from, or purified away from other cells of the organism in which the cell naturally occurs. Isolated cells can be, for example, at least 99%, at least 98%, at least 95%, at least 90%, at least 85%, or at least 80% pure. Leukocyte: Cells in the blood, also termed “white cells,” that are involved in defending the body against infective organisms and foreign substances. Leukocytes are produced in the bone marrow. There are 5 main types of white blood cell, subdivided between 2 main groups: polymorphonuclear leukocytes (neutrophils, eosinophils, basophils) and mononuclear leukocytes (monocytes and lymphocytes). Lymphocyte antigen 6 family member H (Ly6H): A phosphatidyl inositol-anchored glycoprotein that is member of the Ly6 superfamily of GPI-linked cell surface molecules. Ly6H may be differentially expressed on B cells stimulated with lipopolysaccharide and selectively expressed on plasma cells within the B cell lineage. An exemplary amino acid sequence for Ly6H, and a nucleic acid sequence encoding Ly6H, is provided in GENBANK® AB_012293, February 5, 1999, incorporated herein by reference. Mammal: This term includes both human and non-human mammals. Similarly, the term “subject” includes both human and veterinary subjects. Natural Killer (NK) cells: NK cells are innate lymphoid cells that are large granular lymphocytes (LGL) and are differentiated from the common lymphoid progenitor-generating B and T lymphocytes. NK cells are known to differentiate and mature in the bone marrow, lymph nodes, spleen, tonsils, and thymus. NK cells do not express T-cell antigen receptors (TCR) or pan T marker CD3 or surface immunoglobulins (Ig) B cell receptors, but they usually express the surface markers CD16 (FcγRIII) and CD56 in humans, NK1.1 or NK1.2 in C57BL / 6 mice. NKp46 cell surface marker is expressed in humans, several strains of mice and in monkey species. Nucleic acid: A polymer composed of nucleotide units (ribonucleotides, deoxyribonucleotides, related naturally occurring structural variants, and synthetic non-naturally occurring analogs thereof) linked via phosphodiester bonds, related naturally occurring structural variants, and synthetic non-naturally occurring analogs thereof. Thus, the term includes nucleotide polymers in which the nucleotides and the linkages between them include non-naturally occurring synthetic analogs, such as, for example and without limitation, phosphorothioates, phosphoramidates, methyl phosphonates, chiral-methyl phosphonates, 2-O- methyl ribonucleotides, peptide-nucleic acids (PNAs), and the like. Such polynucleotides can be synthesized, for example, using an automated DNA synthesizer. The term “oligonucleotide” typically refers to short polynucleotides, generally no greater than about 50 nucleotides. It will be understood that when a nucleotide sequence is represented by a DNA sequence (i.e., A, T, G, C), this also includes an RNA sequence (i.e., A, U, G, C) in which “U” replaces “T”. Conventional notation is used herein to describe nucleotide sequences: the left-hand end of a single- stranded nucleotide sequence is the 5'-end; the left-hand direction of a double-stranded nucleotide sequence is referred to as the 5'-direction. The direction of 5' to 3' addition of nucleotides to nascent RNA transcripts is referred to as the transcription direction. The DNA strand having the same sequence as an mRNA is referred to as the “coding strand;” sequences on the DNA strand having the same sequence as an mRNA transcribed from that DNA and which are located 5' to the 5'-end of the RNA transcript are referred to as “upstream sequences;” sequences on the DNA strand having the same sequence as the RNA and which are 3' to the 3' end of the coding RNA transcript are referred to as “downstream sequences.” “cDNA” refers to a DNA that is complementary or identical to an mRNA, in either single stranded or double stranded form. “Encoding” refers to the inherent property of specific sequences of nucleotides in a polynucleotide, such as a gene, a cDNA, or an mRNA, to serve as templates for synthesis of other polymers and macromolecules in biological processes having either a defined sequence of nucleotides (i.e., rRNA, tRNA and mRNA) or a defined sequence of amino acids and the biological properties resulting therefrom. Thus, a gene encodes a protein if transcription and translation of mRNA produced by that gene produces the protein in a cell or other biological system. Both the coding strand, the nucleotide sequence of which is identical to the mRNA sequence and is usually provided in sequence listings, and non-coding strand, used as the template for transcription, of a gene or cDNA can be referred to as encoding the protein or other product of that gene or cDNA. Unless otherwise specified, a "nucleotide sequence encoding an amino acid sequence" includes all nucleotide sequences that are degenerate versions of each other and that encode the same amino acid sequence. Nucleotide sequences that encode proteins and RNA may include introns. The nucleotides can be ribonucleotides, deoxyribonucleotides, or modified forms of either nucleotide. The term includes single- and double- stranded forms of DNA. Pharmaceutically acceptable carriers: The pharmaceutically acceptable carriers of use are conventional. Remington’s Pharmaceutical Sciences, by E. W. Martin, Mack Publishing Co., Easton, PA, 19th Edition, 1995, describes compositions and formulations suitable for pharmaceutical delivery of the disclosed humanized monoclonal antibodies and antigen binding fragments thereof. The nature of the carrier may depend on the particular mode of administration being employed. For instance, parenteral formulations usually comprise injectable fluids that include pharmaceutically and physiologically acceptable fluids such as water, physiological saline, balanced salt solutions, aqueous dextrose, glycerol or the like as a vehicle. For solid compositions (e.g., powder, pill, tablet, or capsule forms), conventional non-toxic solid carriers can include, for example, pharmaceutical grades of mannitol, lactose, starch, or magnesium stearate. In addition to biologically neutral carriers, pharmaceutical compositions to be administered can contain minor amounts of non-toxic auxiliary substances, such as wetting or emulsifying agents, preservatives, and pH buffering agents and the like, for example sodium acetate or sorbitan monolaurate. In particular examples, the carrier is sterile, and / or suspended or otherwise contained in a unit dosage form containing one or more measured doses of the composition. The unit dosage form may be, for example, in a sealed vial, a syringe for injection into a subject, lyophilized for subsequent solubilization and, or in a solid or controlled release dosage. Plasmablast: An immature, short lived plasma CD19+CD138+ cell, called a plasmablast, that is generated in an extrafollicular response to T cell-dependent antigens, or antigens that only stimulate B cells without help from T cells. Plasmablasts produce a substantial proportion of the antibodies associated with an immune response. As they differentiate, a plasmablast begins expressing higher levels of CD27 and CD38. Whereas mature plasmablasts express CD20, early plasmablasts may or not express this marker. Mature plasmablasts include proliferating cells. In humans, additional markers of plasmablasts are CXCR3, HLA-DR, KLF4, MKI67, and MS4A1 (see Miller-Rodes et al., “A Guide to Plasma Cell Markers: An Overview of Characteristic Proteins Used in Identifying Plasma Cells,” available at the Biocompare website, Article 585833, May 16, 2022). Programmed Death (PD)-1: A protein that forms a complex with PD-L1 or PD-L2 protein and is involved in an immune response, such as the co-stimulation of T cells. Generally, PD-1 proteins are substantially identical to the naturally occurring (wild type) PD-1 (see, for example, Ishida et al. EMBO J. 11:3887-3895, 1992, Shinohara et al. Genomics 23:704-706, 1994; and U.S. Patent No.5,698,520, all incorporated by reference herein in their entirety). In several examples, PD-1 signaling reduces, for example, CD8+ T cell cytotoxicity by reducing T cell proliferation, cytokine production, or viral clearance. Exemplary amino acid sequences for PD-1 are provided in GENBANK® Accession Nos. NP_054862.1 (human), NP_068693.1 (mouse) and NP_001178883.1 (rat), which are incorporated herein by reference. Exemplary sequences are also provided in GENBANK® Accession No. NG_012110.1, August 31, 2020, incorporated herein by reference. Rheumatic disease: A group of diseases that affect the musculo-skeletal and connective tissues of the body. These diseases are characterized by chronic inflammation that often leads to permanent tissue damage, deformity, atrophy and disability. Rheumatic diseases affect the joints, bone, soft tissue, or spinal cord, and are classified as inflammatory rheumatism, degenerative rheumatism, extra-articular rheumatism, or collagen diseases. Some rheumatic diseases are known to be autoimmune diseases caused by a subject’s altered immune response. Rheumatoid arthritis is a progressive rheumatic disease, affecting approximately 2% of the adult population of developed countries (Utsinger, P. D., et al., 1985 Rheumatoid Arthritis, p.140). This disease is characterized by persistent inflammatory synovitis that causes destruction of cartilage and bone erosion, leading to structural deformities in the peripheral joints. The symptoms associated with rheumatoid arthritis include joint swelling, joint tenderness, inflammation, morning stiffness, and pain, especially upon flexing. Subjects having advanced stages of arthritis suffer from structural damage, including joint destruction with bone erosion (in: “Principals of Internal Medicine, Harrison, 13thedition, pages 1648-1655). Sjogren’s syndrome is a rheumatic disease. Sjögren’s Syndrome: An autoimmune disease that affects the body's moisture-producing glands (lacrimal and salivary), and often seriously affects other organ systems, such as the lungs, kidneys, and nervous system. The primary symptoms are dryness (dry mouth and dry eyes), pain and fatigue. Other symptoms can include dry skin, vaginal dryness, a chronic cough, numbness in the arms and legs, feeling tired, muscle and joint pains, and thyroid problems. Those affected are also at an increased risk (15%) of lymphoma. Smith (Sm) Antigen: A nuclear protein complex consisting of a group of core proteins. The proteins SmB1 (SmB), SmB2 (SmB’), SmB3 (SmN), SmD1, SmD2, SmD3, SmE, SmF and SmG, have been identified in this complex, and are expressed in the nuclei of all cells. The Sm proteins, together with ribonucleoproteins and small nuclear RNA (snRNA) form an RNA-protein complex or small nuclear ribonucleoprotein (snRNP), which is involved in precursor messenger RNA (mRNA) splicing, a process which ultimately leads to mature mRNA generation. The Sm protein complex binds to the snRNA as a ring- liked structure, hereby protecting the snRNA from degradation by nucleases and supporting RNA- processing. There are different snRNAs that are part of different snRNPs (e.g. U1, U2, U4 / U6 and U5). U1- SnRNP is an example of a well-known spliceosome, which consists of U1-RNA, the ribonucleoproteins RNP70, A and C and Sm Proteins. The Sm proteins are highly conserved in eukaryotes and share highly conserved motifs (Sm motif 1 en motif 2), which are involved in the interactions between the different Sm proteins. Anti-Sm antibodies can be detected in SLE patients. See Joyce et al., J. Transl. Autoimmun.5: 100155 (April 13, 2022). Specifically bind: When referring to an antibody or antigen binding fragment, refers to a binding reaction which determines the presence of a target protein in the presence of a heterogeneous population of proteins and other biologics. Thus, under designated conditions, an antibody binds preferentially to a particular target protein, peptide or polysaccharide (such as an antigen present on a pathogen, such as dengue virus) and does not bind in a significant amount to other proteins present in the sample or subject. Specific binding can be determined by standard methods. See Harlow & Lane, Antibodies, A Laboratory Manual, 2nded., Cold Spring Harbor Publications, New York (2013), for a description of immunoassay formats and conditions that can be used to determine specific immunoreactivity. With reference to an antibody-antigen complex, specific binding of the antigen and antibody has a KD of less than about 10-7Molar, such as less than about 10-8Molar, 10-9, or even less than about 10-10Molar. KD refers to the dissociation constant for a given interaction, such as a polypeptide ligand interaction or an antibody antigen interaction. For example, for the bimolecular interaction of an antibody or antigen binding fragment and an antigen it is the concentration of the individual components of the bimolecular interaction divided by the concentration of the complex. An antibody that specifically binds IL-12 is an antibody that binds substantially to IL-12, IL-12 attached to a substrate, or IL12 in a biological specimen. It is, of course, recognized that a certain degree of non-specific interaction may occur between an antibody or conjugate including an antibody (such as an antibody that specifically binds IL-12 or conjugate including such antibody) and a non-target (such as a sample of from a subject that does not have an autoimmune condition). Typically, specific binding results in a much stronger association between the antibody and protein or cells bearing the antigen than between the antibody and protein or cells lacking the antigen. Specific binding typically results in greater than 2- fold, such as greater than 5-fold, greater than 10-fold, or greater than 100-fold increase in amount of bound antibody (per unit time) to a protein including the epitope or cell or tissue expressing the target epitope as compared to a protein or cell or tissue lacking this epitope. Specific binding to a protein under such conditions requires an antibody that is selected for its specificity for a particular protein. A variety of immunoassay formats are appropriate for selecting antibodies or other ligands specifically immunoreactive with a particular protein. For example, solid-phase ELISA immunoassays are routinely used to select monoclonal antibodies specifically immunoreactive with a protein. Subject: Living multi-cellular vertebrate organisms, a category that includes human and non- human mammals. In some examples, the subject is a mammalian subject, for example, a human, non-human primate, canine, or feline. In a non-limiting example, the subject is a human. In a particular example, the subject has an autoimmune disease. In an additional example, a subject is selected that needs inhibition treatment, such as a subject with an autoimmune disease. Systemic Lupus Erythematosus (SLE): An autoimmune disease in which the immune system attacks tissues in many parts of the body. Common symptoms include painful and swollen joints, fever, chest pain, hair loss, mouth ulcers, swollen lymph nodes, feeling tired, and a red rash which is most commonly on the face. In SLE, the immune system produces antibodies against self-protein, particularly against proteins in the cell nucleus. It most commonly begins between the ages of 15 and 45, but a wide range of ages can be affected. Women of childbearing age and those of African, Caribbean, and Chinese descent are at higher risk. Skin symptoms are apparent in about 70% of people with SLE. The three main categories of lesions are chronic cutaneous (discoid) lupus, subacute cutaneous lupus, and acute cutaneous lupus. People with discoid lupus may exhibit thick, red scaly patches on the skin. Similarly, subacute cutaneous lupus manifests as red, scaly patches of skin but with distinct edges. Acute cutaneous lupus manifests as a rash. Some have the classic malar rash (commonly known as the butterfly rash) associated with the disease. People with SLE have intense polyclonal B-cell activation, with a population shift towards immature B cells. Memory B cells with increased CD27+ / IgD- are less susceptible to immunosuppression. CD27- / IgD- memory B cells are associated with increased disease activity and renal lupus. T cells, which regulate B-cell responses and infiltrate target tissues, have defects in signaling, adhesion, co-stimulation, gene transcription, and alternative splicing. Therapeutic agent: Used in a generic sense, it includes treating agents, prophylactic agents, and replacement agents. A therapeutic agent is used to ameliorate a specific set of conditions in a subject with a disease or a disorder, such as an autoimmune disease. T-bet: An immune cell transcription factor, also known as Tbx21, that was originally described as the master regulator of Th1 cell development. However, T-bet is now recognized to have a role in both the adaptive and innate immune systems. T-bet directs T-cell homing to pro-inflammatory sites by the regulation of CXCR3 expression. An exemplary amino acid sequence of T-bet, and a nucleic acid sequence encoding T-bet, is provided in GENBANK Accession No. NG_012166, December 3, 2021, incorporated herein by reference. T Cell: A white blood cell critical to the immune response. Generally, mature T cells express CD3. T cells include, but are not limited to, CD4+T cells and CD8+T cells. A CD4+T lymphocyte is an immune cell that carries a marker on its surface known as cluster of differentiation 4 (CD4). CD4 cells, classically known as helper T cells (Th cells), help orchestrate the immune response, including antibody responses and killer T cell responses. CD8+T cells carry the cluster of differentiation 8 (CD8) marker. In one aspect, CD8 T cells are cytotoxic T lymphocytes (Tc cells) which are capable of lysing target cells by direct cell contact. These cells play a role in the elimination of virus-infected cells and tumor cells and are involved in transplant rejection processes. However, in other aspects, a CD8 cell can function as a suppressor T cell. V-domain Ig suppressor of T cell activation (VISTA): A potent negative regulator of T-cell function that is expressed on hematopoietic cells. VISTA levels are heightened within the tumor microenvironment, in which its blockade can enhance antitumor immune responses in mice and humans. The structure of human VISTA, and it function in lymphocyte negative regulation in cancer, have been determined (see Lines et al., Cancer Res.74: 1924-32, 2014). An exemplary amino acid sequence, and nucleic acid sequence encoding VISTA, are provided in GENBANK Accession No. NG_008835, June 1, 2023, incorporated herein by reference. Selection of a Subject for Treatment It is disclosed herein that subjects with an autoimmune disease can be selected for treatment with an IL-12 antagonist. In some aspects, the autoimmune disease is a systemic autoimmune disease. In other aspects, the autoimmune disease is a rheumatoid disease. In some aspects, the autoimmune disease is systemic lupus erythematosus (SLE). In other aspects, the autoimmune disease is Sjogren’s syndrome. In more aspects, the subject HAS SLE, and has nephritis and / or skin disease. The subject can be a mammal, such as a human or a veterinary subject. In aspects, the methods include selecting a subject with the autoimmune disease that has i) an increase in ABC, DN1 cells, DN2 cells, DN3 cells, and / or plasmablasts in a biological sample obtained from the subject as compared a control, ii) an increase of T-bet, CXCR3, CD326, VISTA, Ly6H, CD317 and / or IFNγ expressing lymphocytes in a biological sample obtained from the subject as compared to a control; iii) elevated serum concentration of IL-12 and / or IFNγ as compared to a control, and / or iv) elevated anti-RNA or anti-Smith (SM) antibodies in a biological sample obtained from the subject as compared to a control. The biological sample can be a blood sample, or any biological sample including B cells. a. Detection of Cells In aspects, the disclosed methods include selecting a subject with the autoimmune disease that has i) an increase in DN1 cells, DN2 cells, DN3 cells, and / or plasmablasts in a biological sample obtained from the subject as compared a control and / or selecting a subject that has ii) an increase of T-bet, CXCR3, CD326, VISTA, Ly6H, CD317 and / or IFNγ expressing lymphocytes in a biological sample obtained from the subject as compared to a control. In certain aspects, the method includes measuring DN1 cells, DN2 cells, DN3 cells, and / or plasmablasts cells in a biological sample obtained from the subject. An increase in the presence of ABC cells as compared to a control indicates that the subject can be treated with the IL-12 antagonist. In some aspects, the control is the amount of DN1 cells, DN2 cells, DN3 cells, and / or plasmablasts cells in a biological sample obtained from a subject that does not have the autoimmune disease. In other aspects, the control is a standard value. DN cells are CD19+ CD27- IgD- B lymphocytes. In some aspects, the method includes measuring CD19+ CD27- IgD- B lymphocytes. DN1 cells are CD19+ CD27- IgD- CD11c(+ or -) CXCR5+ B lymphocytes. Thus, in some aspects, the method includes measuring CD19+ CD27- IgD- CD11c(+ or - )CXCR5+ lymphocytes. DN2 B cells are CD19+ CD27- IgD- CD11c+ CXCR5-. In some aspects, the method includes measuring CD19+ CD27- IgD- CD11c+ CXCR5- lymphocytes. DN3 cells are CD19+ CD27- IgD- CD11c- CXCR5- B lymphocytes. Thus, in some aspects, the method includes measuring CD19+ CD27- IgD- CD11c- CXCR5- B lymphocytes. The method can include measuring DN1 and DN2 cells. The method can include measuring DN2 and DN3 cells. The method can include measuring DN1 and DN3 cells. The method can include measuring ABC, DN1, DN2, and DN3 cells. In other aspects, the method includes measuring DN1 cells in a biological sample obtained from the subject. An increase in the presence of DN1 cells as compared to a control indicates that the subject can be treated with the IL-12 antagonist. In some aspects, the control is the amount of DN1 cells in a biological sample obtained from a subject that does not have the autoimmune disease. In other aspects, the control is a standard value. In more aspects, the method includes measuring DN2 cells in a biological sample obtained from the subject. An increase in the presence of DN2 cells as compared to a control indicates that the subject can be treated with the IL-12 antagonist. In some aspects, the control is the amount of DN2 cells in a biological sample obtained from a subject that does not have the autoimmune disease. In other aspects, the control is a standard value. In further aspects, the method includes measuring DN3 cells in a biological sample obtained from the subject. An increase in the presence of DN3 cells as compared to a control indicates that the subject can be treated with the IL-12 antagonist. In some aspects, the control is the amount of DN3 cells in a biological sample obtained from a subject that does not have the autoimmune disease. In other aspects, the control is a standard value. In aspects, an increase in ABC, DN1, DN2, and / or DN3 cells in the biological sample obtained from the subject of at least about 20%, at least about 25%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 90%, at least about 100%, at least about 125%, at least about 150%, or at least about 200%, or at least about 300%, at least about 400%, or at least about 500% with respect to the control indicates that the subject can be treated with the IL-12 antagonist. Plasmablast cells are CD19+ CD138+ cells. The disclosed methods can include measuring CD19+CD138+ cells. CD19+ CD138+ cells include CD19+ CD27+ CD38+ CD20- cells and CD19+ CD38+ IRF4-high cells. The disclosed methods can include measuring CD19+ CD138+ cells, such as CD19+ CD27+ CD38+ CD20- cells and / or CD19+ CD38+ IRF4-high cells. In more aspects, the method includes measuring plasmablasts in a biological sample obtained from the subject. An increase in the presence of plasmablasts as compared to a control indicates that the subject can be treated with the IL-12 antagonist. In some aspects, the control is the amount of plasmablasts in a biological sample obtained from a subject that does not have the autoimmune disease. In other aspects, the control is a standard value. In some aspects, the method includes measuring CD19+ CD138+ cells. In other aspects, the method includes measuring CD19+ CD27+ CD38+ CD20- cells. In further aspects, the method includes measuring CD19+ CD38+ IRF4-high cells. In aspects, an increase in plasmablasts in the biological sample obtained from the subject of at least about 20%, at least about 25%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 90%, at least about 100%, at least about 125%, at least about 150%, or at least about 200%, or at least about 300%, at least about 400%, or at least about 500% with respect to the control indicates that the subject can be treated with the IL-12 antagonist. These cells can be CD19+ CD138+ cells, such as CD19+ CD27+ CD38+ CD20- cells and / or CD19+ CD38+ IRF4-high cells. In other aspects, the method includes measuring T-bet expressing lymphocytes in a biological sample obtained from the subject. An increase in the presence of T-bet expressing lymphocytes as compared to a control indicates that the subject can be treated with the IL-12 antagonist. In some aspects, the control is the amount of T-bet expressing lymphocytes in a biological sample obtained from a subject that does not have the autoimmune disease. In other aspects, the control is a standard value. In some aspects, the T-bet expressing lymphocytes are CD4+ T-bet+ or CD4+Tbet+IFNγ+ cells. In some aspects, the T-bet expressing lymphocytes are Th1 cells. In other aspects, these cells are B cells that express T-bet. In yet more aspects, the method includes measuring CXCR3 expressing lymphocytes in a biological sample obtained from the subject. An increase in the number of CXCR3 expressing lymphocytes as compared to a control indicates that the subject can be treated with the IL-12 antagonist. In some aspects, the control is the amount of CXCR3 expressing lymphocytes in a biological sample obtained from a subject that does not have the autoimmune disease. In other aspects, the control is a standard value. In other aspects, the method comprises measuring CD326 expressing lymphocytes in a biological sample obtained from the subject. An increase in the presence of CD326 expressing lymphocytes as compared to a control indicates that the subject can be treated with the IL-12 antagonist. In some aspects, the control is the amount of CD326 expressing lymphocytes in a biological sample obtained from a subject that does not have the autoimmune disease. In other aspects, the control is a standard value. In other aspects, the method comprises measuring VISTA expressing lymphocytes in a biological sample obtained from the subject. An increase in the presence of VISTA expressing lymphocytes as compared to a control indicates that the subject can be treated with the IL-12 antagonist. In some aspects, the control is the amount of VISTA expressing lymphocytes in a biological sample obtained from a subject that does not have the autoimmune disease. In other aspects, the control is a standard value. In further aspects, the method includes measuring Ly6H expressing lymphocytes in a biological sample obtained from the subject. An increase in the presence of Ly6H expressing lymphocytes as compared to a control indicates that the subject can be treated with the IL-12 antagonist. In some aspects, the control is the amount of Ly6H expressing lymphocytes in a biological sample obtained from a subject that does not have the autoimmune disease. In other aspects, the control is a standard value. In yet other aspects, method includes measuring CD317 expressing lymphocytes in a biological sample obtained from the subject. An increase in the presence of CD317 expressing lymphocytes as compared to a control indicates that the subject can be treated with the IL-12 antagonist. In some aspects, the control is the amount of CD317 expressing lymphocytes in a biological sample obtained from a subject that does not have the autoimmune disease. In other aspects, the control is a standard value. In other aspects, the method comprises measuring IFNγ expressing lymphocytes in a biological sample obtained from the subject. An increase in the presence of IFNγ expressing lymphocytes as compared to a control indicates that the subject can be treated with the IL-12 antagonist. In some aspects, the control is the amount of IFNγ expressing lymphocytes in a biological sample obtained from a subject that does not have the autoimmune disease. In other aspects, the control is a standard value. In aspects, an increase in T-bet, CXCR3, CD326, VISTA, Ly6H, CD317 and / or IFNγ expressing lymphocytes in the biological sample obtained from the subject of at least about 20%, at least about 25%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 90%, at least about 100%, at least about 125%, at least about 150%, or at least about 200%, or at least about 300%, at least about 400%, or at least about 500% with respect to the control indicates that the subject can be treated with the IL-12 antagonist. The method can include measuring 1, 2, 3, 4, 5, 6, or all 7 of these types of cells. Methods for isolating, detecting, and measuring specific population of lymphocytes, including B and T cells, are known in the art, and exemplary protocols are provided in the Examples section. These methods generally involve the use of molecular and / or biochemical techniques and not simple visual observation. In some examples, fluorescence activated cell sorting (FACS) is utilized. FACS can be used to sort (isolate) cells such as B cells or plasmablasts, by contacting the cells with an appropriately labeled antibody. In one aspect, several antibodies (such as antibodies that bind CD27, CD20, CD19, CD38, CD138, CD11c, CD4, T-bet, CXCR3, CD326, VISTA, Ly6H, CD317, IFNγ and / or IgD) and FACS sorting can be used to produce substantially purified populations of B cells and / or plasmablasts, which are measured to select subjects of interest. In some aspects, selected subjects are further treated with an IL-12 antagonist. FACS employs a plurality of color channels, low angle and obtuse light-scattering detection channels, and impedance channels, among other more sophisticated levels of detection, to separate or sort cells. Any FACS technique can be employed as long as it is not detrimental to the viability of the desired cells. (For exemplary methods of FACS see U.S. Patent No.5, 061,620). However, other techniques of differing efficacy can be employed to purify and isolate desired populations of cells. The separation techniques employed should maximize the retention of viability of the fraction of the cells to be collected. The particular technique employed will, of course, depend upon the efficiency of separation, cytotoxicity of the method, the ease and speed of separation, and what equipment and / or technical skill is required. Separation procedures include magnetic separation, using antibody-coated magnetic beads, affinity chromatography, cytotoxic agents, either joined to a monoclonal antibody or used in conjunction with complement, and "panning," which utilizes a monoclonal antibody attached to a solid matrix, or another convenient technique. Antibodies attached to magnetic beads and other solid matrices, such as agarose beads, polystyrene beads, hollow fiber membranes and plastic petri dishes, allow for direct separation. Cells that are bound by the antibody can be removed from the cell suspension by simply physically separating the solid support from the cell suspension. The exact conditions and duration of incubation of the cells with the solid phase-linked antibodies will depend upon several factors specific to the system employed. The selection of appropriate conditions, however, is well within the skill in the art. The unbound cells then can be eluted or washed away with physiologic buffer after sufficient time has been allowed for the cells expressing a marker of interest (e.g., CD19, CD20, CD38 or CD138) to bind to the solid-phase linked antibodies. The bound cells are then separated from the solid phase by any appropriate method, depending mainly upon the nature of the solid phase and the antibody employed. Antibodies can be conjugated to biotin, which then can be removed with avidin or streptavidin bound to a support, or fluorochromes, which can be used with a fluorescence activated cell sorter (FACS), to enable cell enumeration and / or separation. For example, cells expressing markers of interest, such as CD19 can be initially separated from other cells by the cell-surface expression. The marker CD19 is specific to the B cell lineage. FACS can then be used to further detect cell populations of interest. In some aspects, the methods include detecting an increase in ABC, DN1 cells, DN2 cells, DN3 cells, and / or plasmablasts in a blood sample obtained from the subject as compared a control. The method can include detecting an increase in DN1 cells in a blood sample obtained from the subject as compared a control. The method can include detecting an increase in DN2 cells in a blood sample obtained from the subject as compared a control. The method can include detecting an increase in DN3 cells in a blood sample obtained from the subject as compared a control. The method can include detecting an increase in plasmablasts in a blood sample obtained from the subject as compared a control. The method can include detecting an increase in 1, 2, 3 or all 4 of DN1 cells, DN2 cells, DN3 cells, and plasmablasts as compared to a control. These cells can be detecting using FACS. The control can be a standard value, or the amount of DN1 cells, DN2 cells, DN3 cells, and plasmablasts, respectively, in a biological sample obtained from one or more subjects that do not have the autoimmune disease, such as healthy subjects. In further aspects, the methods include treating the selected subject with the IL-12 antagonist, as disclosed herein. Double negative (DN) B cells, also called ABC cells, express CD19, but do not express IgD or CD27, and thus are CD19+CD27-IgD- (see Jenks et al., Immunity 49(4): 725-736, 2018). DN1 B cells are CD19+ CD27- IgD- CD11c(+ or -)CXCR5+ (see Jenks et al., Immunity 49(4): 725-736, 2018). DN2 B cells are CD19+ CD27- IgD- CD11c+ CXCR5-. DN3 B cells are CD19+ CD27- IgD- CD11c- CXCR5- (see Chamard et al., Cell Reports 42: 12630, June 27, 2023). These cells can readily be measured using FACS. Thus, one or more of these cell types can be measured. In some aspects, the methods include obtaining a biological sample obtained from the subject, such as a blood sample, and separating cells that are CD19+CD27-IgD-, and evaluating the expression of CD11c and CXCR5, to detect the amount of DN1, DN2 and / or DN3 cells in the biological sample. Plasmablasts also can be detected by FACS. In some aspects, the methods include measuring CD19+CD138+ plasmablasts in a biological sample obtained from the subject. In other aspects, the methods include measuring CD19+CD27+CD38+ plasmablasts in a biological sample obtained from the subject. In other aspects, the methods include measuring CD19+CD38+IRF4-high plasmablasts in a biological sample obtained from the subject. These methods can also include treating the subject with an IL- 12 antagonist. The method can include detecting an increase in plasmablasts as compared to a control. The control can be a standard value, or the amount of plasmablasts in a biological sample obtained from one or more subjects that do not have the autoimmune disease, such as healthy subjects. These methods can also include treating the subject with an IL-12 antagonist. In other aspects, the methods include detecting an increase in T-bet, CXCR3, CD326, VISTA, Ly6H, CD317 and / or IFNγ expressing lymphocytes as compared to a control. These cells can also be detected by FACS. In some aspects, the methods include measuring T-bet expressing lymphocytes in a biological sample obtained from the subject. In other aspects, the methods include measuring CXCR3 expressing lymphocytes in a biological sample obtained from the subject. In other aspects, the methods include measuring CD326 expressing lymphocytes in a biological sample obtained from the subject. In other aspects, the methods include measuring VISTA expressing lymphocytes in a biological sample obtained from the subject. In other aspects, the methods include measuring Ly6H expressing lymphocytes in a biological sample obtained from the subject. In other aspects, the methods include measuring CD317 expressing lymphocytes in a biological sample obtained from the subject. In other aspects, the methods include measuring IFNγ expressing lymphocytes in a biological sample obtained from the subject. The methods can include detecting 1, 2, 3, 4, 5, 6 or all of T-bet, CXCR3, CD326, VISTA, Ly6H, CD317 and / or IFNγ expressing lymphocytes in a biological sample obtained from the subject. These cells can be detected using FACS. T-bet, CXCR3, CD326, VISTA, Ly6H, CD317 and / or IFNγ expressing lymphocytes also can be detected by FACS. Exemplary methods are disclosed in the Examples section below. The control can be a standard value, or the amount of T-bet, CXCR3, CD326, VISTA, Ly6H, CD317 and / or IFNγ expressing lymphocytes, respectively, in a biological sample obtained from one or more subjects that do not have the autoimmune disease, such as healthy subjects. In further aspects, the methods include treating the selected subject with the IL-12 antagonist, as disclosed herein. These methods can also include treating the subject with an IL-12 antagonist. Methods for analyzing B cell proliferation are known in the art. For example, membrane dye dilution approaches can be utilized which include ex vivo chemical labeling of cells of interest with fluorescent dyes. Labeling with tritiated nucleoside analogues (commonly3H-thymidine deoxyribonucleoside,3H-TdR) or bromodeoxyuridine (BrdU) can be utilized. FACS analysis is available for the measurement of BrdU incorporation. Surrogate markers of proliferation such as DNA content and cell cycle-associated proteins, can also be used. In one example, measurement of Ki67 or PCNA can be utilized. Ki67 antigen is the prototypic cell cycle related nuclear protein that is expressed by proliferating cells in all phases of the active cell cycle (G1, S, G2 and M phase). It is absent in resting (G0) cells. Ki67 antibodies are useful in establishing proliferation. Ki67 antibodies can be used to quantify proliferating cells among and resting cells (Ki67 index). Ki67 is routinely used as a marker of cell cycling and proliferation; antibodies to Ki67 are commercially available, such as from ABCAM®, and methods are available to use these antibodies in immunohistochemical and FACS analyses. Other methods can be used to detect those cells that are in the active cell cycle at the time of sampling. Proliferation of lymphocytes, such as B cells, can also be measured by using methods that utilize stable isotopes to label DNA in biological samples including cells. DNA is uniformly and highly labeled via the de novo synthesis pathway. The stable isotope labels used, e.g.,2H-glucose or heavy water (2H2O or H218O), are non-toxic to animals and humans, and generally regarded as safe by the US Food and Drug Administration (FDA) (see U.S. Patent Application Publication No.2009 / 0155179). The measurement of stable isotope label incorporation into lymphocyte DNA comprises the following steps: (i) extraction of DNA or its release from chromatin without further isolation, hydrolysis of DNA to deoxyribonucleotides, (ii) selective release of deoxyribose from purine deoxyribonucleotides, (iii) derivatization of purine deoxyribose to a volatile derivative (e.g., pentane tetraacetate, pentafluorobenzyl tetraacetyl derivative, or another suitable derivative) suitable for analysis by gas chromatography / mass spectrometry (GC / MS), (iv) GC / MS analysis of said derivative, (v) analysis of the pattern of mass isotopomer abundance of said derivative, and (vi) calculation from said pattern of an excess enrichment value that is a measure of stable isotope incorporation. Specific aspects of each of these methods have been taught (see U.S. Pat. No. 5,910,40). b. Detection of Serum Concentrations of IL-12 and IFNγ In other aspects, the method can include detecting elevated serum concentration of IL-12 and / or IFNγ as compared to a control. In some examples, a serum sample is used without processing. In other examples, a serum sample is processed prior to protein analysis, for example by adding one or more components (such as detergents, buffers, or salts), lysis (if cells are present), and / or fractionation. Any standard immunoassay format (such as ELISA, Western blot, or radioimmunoassay) can be used to measure levels of IL-12 or IFNγ. Immunohistochemical techniques can also be utilized for protein detection and quantification. General guidance regarding such techniques can be found in Bancroft and Stevens (Theory and Practice of Histological Techniques, Churchill Livingstone, 1982) and Ausubel et al. (Current Protocols in Molecular Biology, John Wiley & Sons, New York, 1998). Kits for the detection of IL-12 and IFNγ are commercially available and include ELISA assays and bioassays, see for example, the Promega website and Axion Biosystems. In some aspects, the control is the serum concentration of IL-12 or IFNγ, respectively a subject that does not have the autoimmune disease. In other aspects, the control is a standard value. In aspects, an increase in the serum concentration of IL-12 and / or IFNγ of at least about 20%, at least about 25%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 90%, at least about 100%, at least about 125%, at least about 150%, or at least about 200%, or at least about 300%, at least about 400%, or at least about 500% with respect to the control indicates that the subject can be treated with the IL-12 antagonist. In some aspects, the methods include contacting a serum from a subject with a monoclonal antibody that specifically binds IL-12 or IFNγ, or an antigen binding fragment thereof, to form an immune complex. The presence (or absence) of the immune complex is then detected. In some examples of the disclosed methods, the monoclonal antibody or antigen binding fragment disclosed herein is conjugated to a detectable marker. In some examples, the methods further include contacting a second antibody that specifically binds the antibody, or antigen binding fragment thereof, for a sufficient amount of time to form an immune complex and detecting this immune complex. In some examples, the second antibody is conjugated to a detectable marker. An increase in the presence of the immune complex, as indicted by an increase in the detectable marker, in a biological sample from the subject, compared to the presence of the immune complex, as indicted by the amount of detectable marker, in a control sample indicates that the subject has increased serum IL-12 or IFNγ. These subjects can be selected for treatment with the IL-12 antagonist. Suitable detectable markers for the humanized monoclonal antibody or secondary antibody are described and known to a practitioner. For example, various enzymes, prosthetic groups, fluorescent materials, luminescent materials, magnetic agents and radioactive materials. Non-limiting examples of suitable enzymes include horseradish peroxidase, alkaline phosphatase, beta-galactosidase, or acetylcholinesterase. Non-limiting examples of suitable prosthetic group complexes include streptavidin / biotin and avidin / biotin. Non-limiting examples of suitable fluorescent materials include umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin. A non-limiting exemplary luminescent material is luminol; a non-limiting exemplary a magnetic agent is gadolinium, and non-limiting exemplary radioactive labels include125I,131I,35S or3H. In some examples, IL-12 or IFNγ (or fragments thereof) can also be detected in a sample using mass spectrometry methods, such as mass spectrometry (MS), tandem MS (MS / MS), matrix-assisted laser desorption / ionization-time of flight (MALDI-TOF) MS, or electrospray ionization (ESI)-MS. In some examples, the sample may be subjected to a separation technique, such as liquid chromatography or 2- dimensional electrophoresis prior to MS analysis. Semi-quantitative or quantitative MS methods are also available. (See, e.g., Gygi et al., Nat. Biotechnol.17:994-999, 1999; Aebersold, J. Inf. Dis.187:S315-S320, 2003.) In other examples, proteins or fragments thereof are identified or confirmed using microarray techniques. In this method, protein of interest or fragments thereof are plated, or arrayed, on a microchip substrate. The arrayed proteins are then contacted with proteins prepared or isolated from the sample. Binding of the proteins from the sample with the arrayed proteins is detected, for example, based on contacting with a label and localization to an addressable location on the array. Microarray analysis can be performed by commercially available equipment, following the manufacturer’s protocols, such as are supplied with PROTOARRAY® protein microarray (Life Technologies) or HUPROT™ arrays (Cambridge Protein Arrays). In other examples, a bead-based assay is used to measure proteins in the sample. Such assays typically include beads coated with a capture antibody for a specific analyte. The beads are incubated with proteins prepared or isolated from a sample and binding of a protein to a bead is detected, for example using flow cytometry. Bead-based assays can be multiplexed, for example by including beads with different fluorescence intensities, each coated with an antibody specific for a specific protein. The presence and identity of different proteins can thus be detected, based on the fluorescence of the particular bead bound by a protein. Bead-based assays are commercially available (such as the Luminex xMAP® technology or the BD Biosciences Cytometric Bead Array). c. Detection of anti-RNA or anti-Smith (SM) antibodies As disclosed in European Patent No. EP0568554A1, methods are available for the quantitation of anti-RNA antibodies in a biological sample from subjects. These methods include contacting the RNA with the biological sample, which causes the formation of an immune complex between RNA and anti-RNA antibodies present in the biological sample, allowing a qualitative and / or quantitative determination of the antibodies reacting with RNA. Similar methods can be used to detect anti-Sm antibodies. The methods include contacting Sm antigen with the biological sample, which causes the formation of an immune complex between the Sm antigen and anti-Sm antibodies present in the biological sample, allowing a qualitative and / or quantitative determination of the antibodies reacting with the Sm antigen. There are various techniques that can be used to detect anti-Sm antibodies. One technique to detect anti-Sm antibodies is immunoprecipitation using a radioactive (e.g.35S-methionine labelled cell extract) immunoassay (RIA). Other techniques, including indirect immunofluorescence tests (IIFT) and antigen- specific (solid-phase) immunoassays, such as enzyme-linked immunosorbent assays (ELISA), addressable laser bead immunoassays (ALBIA), line immunoassays (LIA), chemiluminescent immunoassays (CLIA) and fluorescent enzyme immunoassays (FEIA) also can be used. These antigen specific immunoassays use, either a mixture of Smith antigens or a recombinant Sm antigen, optionally obtained by purification of nuclear extract or produced by in vitro translation, respectively, coated to a solid phase (e.g. plate / well, membrane, bead). Techniques are disclosed, for example, in van Beers et al., J. Transl. Autoimmun.5: 100155, 2022 and Llorente et al., Clin. Chem. Lab. Med.43:748–752, 2005, both incorporated herein by reference). Membranes can be prepared that have RNA and protein antigens, such as Sm antigens, attached that are the targets of autoimmune antibodies. The resulting antibody-antigen complex can be detected using a variety of procedures and reagents that are known in the art. In one aspect, the antibody-antigen complex can be detected using Protein A (or protein G) which binds almost irreversibly to human IgG. The Protein A can be labeled with a signal generating system such as biotin, which is detected using streptavidin coupled to an enzyme such as alkaline phosphatase. The presence of the antibody- antigen-Protein A-biotin- streptavidin-alkaline phosphatase complex is detected through the enzyme's reaction with a substrate that produces a visible band of color on the membrane. Typically, 5-bromo-4-chloro-3-indolyl-phosphate and nitroblue tetrazolium (BCIP / NBT) are used as the substrate for alkaline phosphatase. Other antibody- antigen detection methods include the use of antibodies (of any species) that are reactive with the species of immunoglobulin being detected, examples of which include polyclonal anti-IgG or IgM, monoclonal anti- IgG or IgM, etc., and binding fragments thereof, such as Fab fragment. These anti-Ig antibodies may be labeled with a ligand (e.g., biotin), a hapten (e.g., dinitrophenol) or directly labeled with an enzyme (e.g., alkaline phosphatase, horseradish peroxidase, β-galactosidase, etc.) or a radioisotope (125I, etc.) or any other detectable label. If anti-RNA or anti-Sm antibodies are present in a sample, a distinct permanent "bar code" of bands appears directly on the membrane strip or can be indirectly produced from the membrane strip. Each band on the strip can be assigned to a specific protein-antibody complex. The prominence of the bands in the bar code can be correlated to the titer of the antibody present. Suitable assays are disclosed, for example, in PCT Publication No. WO 1996 / 010748A1, incorporated herein by reference. In aspects, an elevation of anti-RNA antibodies of at least about 20%, at least about 25%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 90%, at least about 100%, at least about 125%, at least about 150%, or at least about 200%, or at least about 300%, at least about 400%, or at least about 500% with respect to the control indicates that the subject can be treated with the IL-12 antagonist. In some aspects, the control is the amount of anti-RNA antibodies a subject that does not have the autoimmune disease. In other aspects, the control is a standard value. In aspects, an elevation of anti-Sm antibodies of at least about 20%, at least about 25%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 90%, at least about 100%, at least about 125%, at least about 150%, or at least about 200%, or at least about 300%, at least about 400%, or at least about 500% with respect to the control indicates that the subject can be treated with the IL-12 antagonist. In some aspects, the control is the amount of anti-Sm antibodies a subject that does not have the autoimmune disease. In other aspects, the control is a standard value. IL-12 and Antagonists Thereof A subject with an autoimmune disorder is selected for treatment using the methods disclosed herein. In some aspects, the disclosed methods include the administration of a therapeutically effective amount of an IL-12 antagonist to the selected subject with an autoimmune disease. IL-12 can bind to the IL-12 receptor expressed on the plasma membrane of cells (e.g., T cells, B cells, NK cells), thereby altering (e.g., initiating, preventing) biological processes. For example, the binding of IL-12 to the IL-12 receptor can stimulate the proliferation of pre-activated T cells and NK cells, enhance the cytolytic activity of cytotoxic T cells (CTL), NK cells and LAK (lymphokine activated killer) cells, induce production of gamma interferon (IFN GAMMA) by T cells and NK cells and induce differentiation of naive Th0 cells into Th1 cells that produce IFN GAMMA and IL-2 (Trinchieri, G., Annual Review of Immunology, 13:251-276 (1995)). In particular, IL-12 is vital for the generation of cytolytic cells (e.g., NK, CTL) and for mounting a cellular immune response (e.g., a Th1 cell mediated immune response). As disclosed herein, IL-12 promotes B cell proliferation and differentiation to plasmablasts by inducing gamma interferon production from B cells (see also (Elsner R.A., and Shlomchik, M.J. Cell Reports 29(9):2796- 2809.e5 (2019), incorporated herein by reference). Thus, IL-12 is important in the generation and regulation of both protective immunity (e.g., eradication of infections) and pathological immune responses (e.g., autoimmunity) (Hendrzak, J. A. and Brunda, M. J., Laboratory Investigation, 72:619-637 (1995)). Accordingly, an immune response can be inhibited using an IL-12 antagonist. IL-12 antagonists include (1) molecules that will bind IL-12 or biologically active fragments thereof, and (2) molecules that will interfere with the binding of IL-12 to receptors or other binding proteins. Antagonists also include RNAi molecules, antisense molecules, and small molecule inhibitors. Antagonists that bind IL-12 include, without limitation, antibodies (mono- or polyclonal) and fragments thereof (including Fab fragments), chimeric antibodies and fragments thereof, IL-12 receptors or fragments thereof, reactive peptides or fragments thereof, and organic small molecules designed to mimic the bioactivity of IL- 12 receptors. Antagonists that interfere with IL-12 binding include, without limitation, chemically or genetically modified peptides of IL-12, subunits of IL-12 and fragments thereof, homopolymers of IL-12 subunits and fragments thereof, and organic small molecules designed to mimic the bioactivity of IL-12. Antagonists that interfere with IL-12 binding interfere with its binding to receptors which induce IFNγ or TNF-α, without inducing the same level of such factors as would binding of IL-12 to the receptor, see U.S. Patent No.8,012,475, incorporated herein by reference. Exemplary antagonists are discussed below. a.. Antibodies Antibodies that specifically bind IL-12 can be produced as disclosed, for example, in U.S. Patent No.8.012,475 and U.S. Patent No.10,519,231. IL-12 is a heterodimeric cytokine consisting of glycosylated polypeptide chains of 35 and 40 kD which are disulfide bonded. In some aspects, the antibody specifically binds the 35 kD component of IL-12. In other aspects, the antibody specifically binds the 40 kD component of IL-12. In more aspects, the antibody specifically binds the bonded 35 kD and 40kD components. In these aspects, the antibody specifically binds IL-12p70. In some aspects, the antibody that specifically binds IL-12 is Ustekinumab. In some aspects, monoclonal IL-12 antibodies can be produced by generation of antibody-producing hybridomas in accordance with known methods (see for example, Goding.1983. Monoclonal antibodies: principles and practice. Academic Press Inc., New York; Yokoyama.1992. “Production of Monoclonal Antibodies” in Current Protocols in Immunology. Unit 2.5. Greene Publishing Assoc. and John Wiley & Sons). Polyclonal sera and antibodies to IL-12 can be produced by inoculation of a mammalian subject with IL-12 or fragments thereof in accordance with known methods. Chizzonite et al., J. Immunol.148, 1992, p. 3117, describes the identification and isolation of an IL-12 receptor. A monoclonal antibody that specifically binds IL-12, or its receptor, can be identified and isolated by screening a recombinant combinatorial immunoglobulin library (such as an antibody phage display library) with IL-12 or its receptor, to isolate immunoglobulin library members that specifically bind the polypeptide. Kits for generating and screening phage display libraries are commercially available (such as, but not limited to, Pharmacia and Stratagene). Examples of methods and reagents particularly amenable for use in generating and screening antibody display library can be found in, for example, by U.S. Pat. No. 5,223,409; PCT Publication No. WO 90 / 02809; PCT Publication No. WO 91 / 17271; PCT Publication No. WO 92 / 18619; PCT Publication WO 92 / 20791; PCT Publication No. WO 92 / 15679; PCT Publication No. WO 92 / 01047; PCT Publication WO 93 / 01288; PCT Publication No. WO 92 / 09690; Barbas et al., Proc. Natl. Acad. Sci. USA 88:79787982, 1991; Hoogenboom et al., Nucleic Acids Res.19:41334137, 1991. Monoclonal antibodies of use in the disclosed methods include the heavy chain (H) complementarity determining regions (HCDR1, HCDR2, and HCDR3) and the light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3) of a monoclonal antibody that specifically binds IL-12, or an antigen binding fragment thereof. In one example the sequence of the specificity determining regions of each CDR is determined. Residues are outside the SDR (non-ligand contacting sites) are substituted. For example, in any of the CDR sequences, at most one, two or three amino acids can be substituted. The production of chimeric antibodies, which include a framework region from one antibody and the CDRs from a different antibody, is well known in the art. For example, humanized antibodies can be routinely produced. The antibody or antibody fragment can be a humanized immunoglobulin having complementarity determining regions (CDRs) from a donor monoclonal antibody that binds IL-12, and immunoglobulin and heavy and light chain variable region frameworks from human acceptor immunoglobulin heavy and light chain frameworks. Generally, the humanized immunoglobulin specifically binds to IL-12 with an affinity constant of at least 107M-1, such as at least 108M-1at least 5 X 108M-1or at least 109M-1. Humanized monoclonal antibodies can be produced by transferring donor complementarity determining regions (CDRs) from heavy and light variable chains of the donor mouse immunoglobulin (such an antibody that specifically binds IL-12) into a human variable domain, and then substituting human residues in the framework regions when required to retain affinity. The use of antibody components derived from humanized monoclonal antibodies obviates potential problems associated with the immunogenicity of the constant regions of the donor antibody. Techniques for producing humanized monoclonal antibodies are described, for example, by Jones et al., Nature 321:522, 1986; Riechmann et al., Nature 332:323, 1988; Verhoeyen et al., Science 239:1534, 1988; Carter et al., Proc. Natl. Acad. Sci. U.S.A.89:4285, 1992; Sandhu, Crit. Rev. Biotech.12:437, 1992; and Singer et al., J. Immunol.150:2844, 1993. The antibody may be of any isotype, but in several aspects the antibody is an IgG, including but not limited to, IgG1, IgG2, IgG3 and IgG4. Chimeric antibodies may also be produced in accordance with known methods. Antibodies that specifically bind IL-12 are disclosed, for example, in U.S. Published Patent Application No.2005 / 0002937, U.S. Patent No.6914128, U.S. Patent No.8,716,449, incorporated herein by reference. In several examples, the antibody specifically binds IL-12 with an affinity constant of at least 107M-1, such as at least 108M-1,at least 5 X 108M-1, or at least 109M-1. In one aspect, the sequence of the humanized immunoglobulin heavy chain variable region framework can be at least about 65% identical to the sequence of the donor immunoglobulin heavy chain variable region framework. Thus, the sequence of the humanized immunoglobulin heavy chain variable region framework can be at least about 75%, at least about 85%, at least about 99% or at least about 95%, identical to the sequence of the donor immunoglobulin heavy chain variable region framework. Human framework regions, and mutations that can be made in humanized antibody framework regions, are known in the art (see, for example, in U.S. Patent No.5,585,089). Antibodies, such as murine monoclonal antibodies, chimeric antibodies, and humanized antibodies, include full length molecules as well as fragments thereof, such as Fab, F(ab')2, and Fv which include a heavy chain and light chain variable region and are capable of binding specific epitope determinants. These antigen binding fragments retain the ability to selectively bind with their antigen. These fragments include: (1) Fab, the fragment which contains a monovalent antigen-binding fragment of an antibody molecule, can be produced by digestion of whole antibody with the enzyme papain to yield an intact light chain and a portion of one heavy chain; (2) Fab', the fragment of an antibody molecule can be obtained by treating whole antibody with pepsin, followed by reduction, to yield an intact light chain and a portion of the heavy chain; two Fab' fragments are obtained per antibody molecule; (3) (Fab')2, the fragment of the antibody that can be obtained by treating whole antibody with the enzyme pepsin without subsequent reduction; F(ab')2 is a dimer of two Fab' fragments held together by two disulfide bonds; (4) Fv, a genetically engineered fragment containing the variable region of the light chain and the variable region of the heavy chain expressed as two chains; and (5) Single chain antibody (such as scFv), defined as a genetically engineered molecule containing the variable region of the light chain, the variable region of the heavy chain, linked by a suitable polypeptide linker as a genetically fused single chain molecule. Methods of making these fragments are known in the art (see for example, Harlow and Lane, Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, New York, 1988). In several examples, the variable region includes the variable region of the light chain and the variable region of the heavy chain expressed as individual polypeptides. Fv antibodies are typically about 25 kDa and contain a complete antigen-binding site with three CDRs per each heavy chain and each light chain. To produce these antibodies, the VH and the VL can be expressed from two individual nucleic acid constructs in a host cell. If the VH and the VL are expressed non-contiguously, the chains of the Fv antibody are typically held together by noncovalent interactions. However, these chains tend to dissociate upon dilution, so methods have been developed to crosslink the chains through glutaraldehyde, intermolecular disulfides, or a peptide linker. Thus, in one example, the Fv can be a disulfide stabilized Fv (dsFv), wherein the heavy chain variable region and the light chain variable region are chemically linked by disulfide bonds. In an additional example, the Fv fragments comprise VH and VL chains connected by a peptide linker. These single-chain antigen binding proteins (scFv) are prepared by constructing a structural gene comprising DNA sequences encoding the VHand VLdomains connected by an oligonucleotide. The structural gene is inserted into an expression vector, which is subsequently introduced into a host cell such as E. coli. The recombinant host cells synthesize a single polypeptide chain with a linker peptide bridging the two V domains. Methods for producing scFvs are known in the art (see Whitlow et al., Methods: a Companion to Methods in Enzymology, Vol.2, page 97, 1991; Bird et al., Science 242:423, 1988; U.S. Patent No.4,946,778; Pack et al., Bio / Technology 11:1271, 1993; and Sandhu, supra). Antibody fragments can be prepared by proteolytic hydrolysis of the antibody or by expression in E. coli of DNA encoding the fragment. Antibody fragments can be obtained by pepsin or papain digestion of whole antibodies by conventional methods. For example, antibody fragments can be produced by enzymatic cleavage of antibodies with pepsin to provide a 5S fragment denoted F(ab')2. This fragment can be further cleaved using a thiol reducing agent, and optionally a blocking group for the sulfhydryl groups resulting from cleavage of disulfide linkages, to produce 3.5S Fab' monovalent fragments. Alternatively, an enzymatic cleavage using pepsin produces two monovalent Fab' fragments and an Fc fragment directly (see U.S. Patent No.4,036,945 and U.S. Patent No.4,331,647, and references contained therein; Nisonhoff et al., Arch. Biochem. Biophys.89:230, 1960; Porter, Biochem. J.73:119, 1959; Edelman et al., Methods in Enzymology, Vol.1, page 422, Academic Press, 1967; and Coligan et al. at sections 2.8.1-2.8.10 and 2.10.1- 2.10.4). Other methods of cleaving antibodies, such as separation of heavy chains to form monovalent light- heavy chain fragments, further cleavage of fragments, or other enzymatic, chemical, or genetic techniques may also be used, so long as the fragments bind to the antigen that is recognized by the intact antibody. Fragments of antibodies, receptors or other reactive peptides can be produced from the corresponding antibodies by cleavage of and collection of the desired fragments in accordance with known methods (see for example, Goding, supra; Andrew et al.1992. “Fragmentation of Immunoglobulins” in Current Protocols in Immunology. Unit 2.8. Greene Publishing Assoc. and John Wiley & Sons). Conservative variants of the antibodies can be produced. Such conservative variants employed in antibody fragments, such as dsFv fragments or in scFv fragments, will retain critical amino acid residues necessary for correct folding and stabilizing between the VHand the VLregions, and will retain the charge characteristics of the residues in order to preserve the low pI and low toxicity of the molecules. Amino acid substitutions (such as at most one, at most two, at most three, at most four, or at most five amino acid substitutions) can be made in the VH and the VL regions to increase yield. In some aspects, these substitutions are made in the framework regions, and are not made in the CDRs. A table of conservative amino acid substitutions is provided above. One of skill in the art can readily review the amino acid sequence of an antibody of interest, locate one or more of the amino acids in the brief table above, identify a conservative substitution, and produce the conservative variant using molecular techniques. Nucleic acid sequences encoding the antibodies can be prepared by any suitable method including, for example, cloning of appropriate sequences or by direct chemical synthesis by methods such as the phosphotriester method of Narang et al., Meth. Enzymol.68:90-99, 1979; the phosphodiester method of Brown et al., Meth. Enzymol.68:109-151, 1979; the diethylphosphoramidite method of Beaucage et al., Tetra. Lett.22:1859-1862, 1981; the solid phase phosphoramidite triester method described by Beaucage & Caruthers, Tetra. Letts.22(20):1859-1862, 1981, for example, using an automated synthesizer as described in, for example, Needham-VanDevanter et al., Nucl. Acids Res.12:6159-6168, 1984; and the solid support method of U.S. Patent No.4,458,066. Chemical synthesis produces a single stranded oligonucleotide. This can be converted into double stranded DNA by hybridization with a complementary sequence, or by polymerization with a DNA polymerase using the single strand as a template. Longer sequences may be obtained by the ligation of shorter sequences generated by chemical synthesis. Exemplary nucleic acids encoding sequences encoding an antagonistic antibody that specifically binds IL-12 can be prepared by cloning techniques. Examples of appropriate cloning and sequencing techniques, and instructions sufficient to direct persons of skill through many cloning exercises are found in Sambrook et al., supra, Berger and Kimmel (eds.), supra, and Ausubel, supra. Product information from manufacturers of biological reagents and experimental equipment also provide useful information. Such manufacturers include the SIGMA Chemical Company (Saint Louis, MO), R&D Systems (Minneapolis, MN), Pharmacia Amersham (Piscataway, NJ), CLONTECH Laboratories, Inc. (Palo Alto, CA), Chem Genes Corp., Aldrich Chemical Company (Milwaukee, WI), Glen Research, Inc., GIBCO BRL Life Technologies, Inc. (Gaithersburg, MD), Fluka Chemica-Biochemika Analytika (Fluka Chemie AG, Buchs, Switzerland), Invitrogen (San Diego, CA), and Applied Biosystems (Foster City, CA), as well as other commercial sources. Nucleic acids can also be prepared by amplification methods. Amplification methods include polymerase chain reaction (PCR), the ligase chain reaction (LCR), the transcription-based amplification system (TAS), the self-sustained sequence replication system (3SR). A wide variety of cloning methods, host cells, and in vitro amplification methodologies are known. In one example, an antibody of use is prepared by inserting the cDNA, which encodes a variable region from the antibody that specifically binds IL-12, into a vector which comprises the cDNA encoding an effector molecule (EM). The insertion is made so that the variable region and the EM are read in frame so that one continuous polypeptide is produced. Thus, the encoded polypeptide contains a functional Fv region and a functional EM region. In one aspect, cDNA encoding a detectable marker (such as an enzyme) is ligated to a scFv so that the marker is located at the carboxyl terminus of the scFv. In another example, a detectable marker is located at the amino terminus of the scFv. In a further example, cDNA encoding a detectable marker is ligated to a heavy chain variable region of an antibody that specifically binds IL-12, so that the marker is located at the carboxyl terminus of the heavy chain variable region. The heavy chain- variable region can subsequently be ligated to a light chain variable region of the antibody that specifically binds IL-12 using disulfide bonds. In a yet another example, cDNA encoding a marker is ligated to a light chain variable region of an antibody that binds IL-12, so that the marker is located at the carboxyl terminus of the light chain variable region. The light chain-variable region can subsequently be ligated to a heavy chain variable region of the antibody that specifically binds IL-12 using disulfide bonds. Once the nucleic acids encoding the antibody or antigen binding fragment thereof are isolated and cloned, the protein can be expressed in a recombinantly engineered cell such as bacteria, plant, yeast, insect and mammalian cells. One or more DNA sequences encoding the antibody or antigen binding fragment thereof can be expressed in vitro by DNA transfer into a suitable host cell. The cell may be prokaryotic or eukaryotic. The term also includes any progeny of the subject host cell. It is understood that all progeny may not be identical to the parental cell since there may be mutations that occur during replication. Methods of stable transfer, meaning that the foreign DNA is continuously maintained in the host, are known. Polynucleotide sequences encoding the antibody or antigen binding fragment thereof (such as an scFv) can be operatively linked to expression control sequences. An expression control sequence operatively linked to a coding sequence is ligated such that expression of the coding sequence is achieved under conditions compatible with the expression control sequences. The expression control sequences include, but are not limited to appropriate promoters, enhancers, transcription terminators, a start codon (i.e., ATG) in front of a protein-encoding gene, splicing signal for introns, maintenance of the correct reading frame of that gene to permit proper translation of mRNA, and stop codons. RNA encoding the disclosed antibodies are also of use. The polynucleotide sequences encoding the antibody or antigen binding fragment thereof can be inserted into an expression vector including, but not limited to a plasmid, virus or other vehicle that can be manipulated to allow insertion or incorporation of sequences and can be expressed in either prokaryotes or eukaryotes. Hosts can include microbial, yeast, insect, and mammalian organisms. Methods of expressing DNA sequences having eukaryotic or viral sequences in prokaryotes are well known in the art. Viral and plasmid DNA vectors capable of expression and replication in a host are known. Transformation of a host cell with recombinant DNA may be carried out by conventional techniques. Where the host is prokaryotic, such as E. coli, competent cells which are capable of DNA uptake can be prepared from cells harvested after exponential growth phase and subsequently treated by the CaCl2 method. Alternatively, MgCl2 can be used. Transformation can also be performed after forming a protoplast of the host cell if desired, or by electroporation. When the host is a eukaryote, such methods of transfection of DNA as calcium phosphate coprecipitates, mechanical procedures such as microinjection, electroporation, insertion of a plasmid encased in liposomes, or virus vectors, may be used. Eukaryotic cells can also be co-transformed with polynucleotide sequences encoding the antibody of antigen binding fragment thereof and a second foreign DNA molecule encoding a selectable phenotype, such as the herpes simplex thymidine kinase gene. Another method is to use a eukaryotic viral vector, such as simian virus 40 (SV40) or bovine papilloma virus, to transiently infect or transform eukaryotic cells and express the protein (see for example, Eukaryotic Viral Vectors, Cold Spring Harbor Laboratory, Gluzman ed., 1982). One of skill in the art can readily use expression systems such as plasmids and vectors of use in producing proteins in cells including higher eukaryotic cells such as the COS, CHO, HeLa and myeloma cell lines. Isolation and purification of a recombinantly expressed polypeptide can be carried out by conventional means including preparative chromatography and immunological separations. Once expressed, the recombinant antibodies can be purified according to standard procedures of the art, including ammonium sulfate precipitation, affinity columns, column chromatography, and the like (see, generally, R. Scopes, Protein Purification, Springer-Verlag, N.Y., 1982). Substantially pure compositions of at least about 90 to 95% homogeneity are disclosed herein, and 98 to 99% or more homogeneity can be used for pharmaceutical purposes. Once purified, partially or to homogeneity as desired, if to be used therapeutically, the polypeptides should be substantially free of endotoxin. Methods for expression of single chain antibodies and / or refolding to an appropriate active form, including single chain antibodies, from bacteria such as E. coli have been described and are applicable to the antibodies disclosed herein. See, Buchner et al., Anal. Biochem.205:263-270, 1992; Pluckthun, Biotechnology 9:545, 1991; Huse et al., Science 246:1275, 1989 and Ward et al., Nature 341:544, 1989. Often, functional heterologous proteins from E. coli or other bacteria are isolated from inclusion bodies and require solubilization using strong denaturants, and subsequent refolding. During the solubilization step, a reducing agent is often used to separate disulfide bonds. An exemplary buffer with a reducing agent is: 0.1 M Tris pH 8, 6 M guanidine, 2 mM EDTA, 0.3 M DTE (dithioerythritol). Reoxidation of the disulfide bonds can occur in the presence of low molecular weight thiol reagents in reduced and oxidized form, as described in Saxena et al., Biochemistry 9: 5015-5021, 1970, incorporated by reference herein, and especially as described by Buchner et al., supra. Renaturation is typically accomplished by dilution (for example, 100-fold) of the denatured and reduced protein into refolding buffer. An exemplary buffer is 0.1 M Tris, pH 8.0, 0.5 M L-arginine, 8 mM oxidized glutathione (GSSG), and 2 mM EDTA. As a modification to the two chain antibody purification protocol, the heavy and light chain regions are separately solubilized and reduced and then combined in the refolding solution. An exemplary yield is obtained when these two proteins are mixed in a molar ratio such that a 5-fold molar excess of one protein over the other is not exceeded. It is desirable to add excess oxidized glutathione or other oxidizing low molecular weight compounds to the refolding solution after the redox-shuffling is completed. In addition to recombinant methods, the antibodies and antigen binding fragments thereof can also be constructed in whole or in part using standard peptide synthesis. Solid phase synthesis of the polypeptides of less than about 50 amino acids in length can be accomplished by attaching the C-terminal amino acid of the sequence to an insoluble support followed by sequential addition of the remaining amino acids in the sequence. Techniques for solid phase synthesis are described by Barany & Merrifield, The Peptides: Analysis, Synthesis, Biology. Vol.2: Special Methods in Peptide Synthesis, Part A. pp. 3-284; Merrifield et al., J. Am. Chem. Soc.85:2149-2156, 1963, and Stewart et al., Solid Phase Peptide Synthesis, 2nd ed., Pierce Chem. Co., Rockford, Ill., 1984. Proteins of greater length may be synthesized by condensation of the amino and carboxyl termini of shorter fragments. Methods of forming peptide bonds by activation of a carboxyl terminal end (such as by the use of the coupling reagent N, N'- dicycylohexylcarbodimide) are known. One anti-IL-12 / 23p40 antibody is ustekinumab (STELARA®) having the heavy chain variable region amino acid sequence of SEQ ID NO:7 as disclosed in U.S. Published Patent Application No 20200197517, and the light chain variable region amino acid sequence of SEQ ID NO:8 as disclosed in U.S. Published Patent Application No 20200197517, and having the heavy chain CDR amino acid sequences of SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO: 3 as disclosed in U.S. Published Patent Application No 20200197517; and the light chain CDR amino acid sequences of SEQ ID NO:4, SEQ ID NO:5, and SEQ ID NO:6 as disclosed in disclosed in U.S. Published Patent Application No 20200197517, incorporated herein by reference. Ustekinumab is of use in the disclosed methods. b. Inhibitory Nucleic Acids Inhibitory nucleic acids that decrease the expression and / or activity of IL-12 can also be used in the methods disclosed herein. In some examples, such inhibitor nucleic acid molecules decrease IL-12 expression or activity by at least 20%, at least 40%, at least 50%, at least 75%, at least 80%, at least 90%, at least 95%, at least 98% or even 100%. One aspect is an RNA interference (RNAi), such as, but not limited to, small inhibitory RNA (siRNA) or short hairpin RNA, which can be used for interference or inhibition of expression of a target. The inhibitory nucleic acid can target IL-12A or IL-12B mRNA. Generally, siRNAs are generated by the cleavage of relatively long double-stranded RNA molecules by Dicer or DCL enzymes (Zamore, Science, 296:1265-1269, 2002; Bernstein et al., Nature, 409:363-366, 2001). In animals and plants, siRNAs are assembled into RISC and guide the sequence specific ribonucleolytic activity of RISC, thereby resulting in the cleavage of mRNAs or other RNA target molecules in the cytoplasm. In the nucleus, siRNAs also guide heterochromatin-associated histone and DNA methylation, resulting in transcriptional silencing of individual genes or large chromatin domains. The present disclosure can include the use of RNA suitable for interference or inhibition of expression of IL-12A or IL-12B, which RNA includes double stranded RNA of about 19 to about 40 nucleotides with the sequence that is substantially identical to a portion of an mRNA or transcript of a target gene, such as IL-12, for which interference or inhibition of expression is desired. For purposes of this disclosure, a sequence of the RNA “substantially identical” to a specific portion of the mRNA or transcript of the target gene for which interference or inhibition of expression is desired differs by no more than about 30%, and in some aspects no more than about 10% or no more than 5% from the specific portion of the mRNA or transcript of the target gene. In particular aspects, the sequence of the RNA is exactly identical to a specific portion of the mRNA or transcript of the target gene (e.g., IL-12A or IL-12B transcripts). Thus, siRNAs disclosed herein include double-stranded RNA of about 15 to about 40 nucleotides in length and a 3’ or 5’ overhang having a length of 0 to 5-nucleotides on each strand, wherein the sequence of the double stranded RNA is substantially identical to (see above) a portion of a mRNA or transcript of a nucleic acid encoding IL-12. In particular examples, the double stranded RNA contains about 19 to about 25 nucleotides, for instance 20, 21, or 22 nucleotides substantially identical to a nucleic acid encoding IL-12. In additional examples, the double stranded RNA contains about 19 to about 25 nucleotides 100% identical to a nucleic acid encoding IL-12A or IL-12B. It should be noted that in this context “about” refers to integer amounts only. In one example, “about” 20 nucleotides refers to a nucleotide of 19 to 21 nucleotides in length. Regarding the overhang on the double-stranded RNA (dsRNA), the length of the overhang is independent between the two strands, in that the length of one overhang is not dependent on the length of the overhang on other strand. In specific examples, the length of the 3’ or 5’ overhang is 0 nucleotides on at least one strand, and in some cases it is 0 nucleotides on both strands (thus, a blunt dsRNA). In other examples, the length of the 3’ or 5’ overhang is 1 nucleotide to 5 nucleotides on at least one strand. More particularly, in some examples the length of the 3’ or 5’ overhang is 2 nucleotides on at least one strand, or 2 nucleotides on both strands. In particular examples, the dsRNA molecule has 3’ overhangs of 2 nucleotides on both strands. Thus, in one particular provided RNA aspect, the double-stranded RNA contains 20, 21, or 22 nucleotides, and the length of the 3’ overhang is 2-nucleotides on both strands. In aspects of the RNAs provided herein, the double-stranded RNA contains about 40-60% adenine+uracil and about 60-40% guanine+cytosine. More particularly, in specific examples the double-stranded RNA contains about 50% AU and about 50% GC. Also disclosed herein are RNAs that further include at least one modified ribonucleotide, for instance in the sense strand of the double-stranded RNA. In particular examples, the modified ribonucleotide is in the 3’ overhang of at least one strand, or more particularly in the 3’ overhang of the sense strand. It is contemplated that examples of modified ribonucleotides include ribonucleotides that include a detectable label (for instance, a fluorophore, such as rhodamine or FITC), a thiophosphate nucleotide analog, a deoxynucleotide (considered modified because the base molecule is ribonucleic acid), a 2’-fluorouracil, a 2’-aminouracil, a 2’-aminocytidine, a 4-thiouracil, a 5-bromouracil, a 5-iodouracil, a 5-(3- aminoallyl)-uracil, an inosine, or a 2’O-Me-nucleotide analog. Antisense and ribozyme molecules for IL-12A or IL-12B are of use in the methods disclosed herein. Antisense nucleic acids are DNA or RNA molecules that are complementary to at least a portion of a specific mRNA molecule (Weintraub, Scientific American 262:40, 1990). In the cell, the antisense nucleic acids hybridize to the corresponding mRNA, forming a double-stranded molecule. The antisense nucleic acids interfere with the translation of the mRNA, since the cell will not translate an mRNA that is double- stranded. Antisense oligomers of about 15 nucleotides can be used, since they are easily synthesized and are less likely to cause problems than larger molecules when introduced into the target cell producing IL-12. The use of antisense methods to inhibit the in vitro translation of genes is known (see, for example, Marcus- Sakura, Anal. Biochem.172:289, 1988). An antisense oligonucleotide can be, for example, about 5, 10, 15, 20, 25, 30, 35, 40, 45 or 50 nucleotides in length. An antisense nucleic acid can be constructed using chemical synthesis and enzymatic ligation reactions. For example, an antisense nucleic acid molecule can be chemically synthesized using naturally occurring nucleotides or variously modified nucleotides designed to increase the biological stability of the molecules or to increase the physical stability of the duplex formed between the antisense and sense nucleic acids, such as phosphorothioate derivatives and acridine substituted nucleotides can be used. Examples of modified nucleotides which can be used to generate the antisense nucleic acid include 5- fluorouracil, 5-bromouracil, 5-chlorouracil, 5-iodouracil, hypoxanthine, xanthine, 4-acetylcytosine, 5- (carboxyhydroxylmethyl) uracil, 5-carboxymethylaminomethyl-2-thiouridin- e, 5- carboxymethylaminomethyluracil, dihydrouracil, beta-D-galactosylqueosine, inosine, amongst others. Use of an oligonucleotide to stall transcription is known as the triplex strategy where an oligonucleotide winds around double-helical DNA, forming a three-strand helix. Therefore, these triplex compounds can be designed to recognize a unique site on a chosen gene (Maher, et al., Antisense Res. and Dev.1(3):227, 1991; Helene, C., Anticancer Drug Design 6(6):569, 1991). This type of inhibitory oligonucleotide is also of use in the methods disclosed herein. Ribozymes, which are RNA molecules possessing the ability to specifically cleave other single- stranded RNA in a manner analogous to DNA restriction endonucleases, are also of use. Through the modification of nucleotide sequences, which encode these RNAs, it is possible to engineer molecules that recognize specific nucleotide sequences in an RNA molecule and cleave it (Cech, J. Amer. Med. Assn. 260:3030, 1988). An advantage of this approach is that because they are sequence-specific only mRNAs with particular sequences are inactivated. There are two basic types of ribozymes namely, tetrahymena-type (Hasselhoff, Nature 334:585, 1988) and “hammerhead”-type. Tetrahymena-type ribozymes recognize sequences which are four bases in length, while “hammerhead”-type ribozymes recognize base sequences 11-18 bases in length. The longer the recognition sequence, the greater the likelihood that the sequence will occur exclusively in the target mRNA species. Consequently, hammerhead-type ribozymes are preferable to tetrahymena-type ribozymes for inactivating a specific mRNA species and 18-base recognition sequences are preferable to shorter recognition sequences. Various delivery systems are known and can be used to administer the siRNAs and other inhibitory nucleic acid molecules as therapeutics. Such systems include, for example, encapsulation in liposomes, microparticles, microcapsules, nanoparticles, recombinant cells capable of expressing the therapeutic molecule(s) (see, e.g., Wu et al., J. Biol. Chem.262, 4429, 1987), construction of a therapeutic nucleic acid as part of a retroviral or other vector, and the like. C. Small Molecule IL-12 Antagonists IL-12 antagonists include molecules that are identified from large libraries of both natural product or synthetic (or semi-synthetic) extracts or chemical libraries according to methods known in the art. The screening methods that detect decreases in IL-12 activity useful for identifying compounds from a variety of sources for activity. The initial screens may be performed using a diverse library of compounds, a variety of other compounds and compound libraries. Thus, molecules that bind IL-12, molecules that inhibit the expression of IL-12A or IL-12B, and molecules that inhibit the activity of IL-12 can be identified. These small molecules can be identified from combinatorial libraries, natural product libraries, or other small molecule libraries. In addition, an IL-12 antagonist can be identified as a compound from commercial sources, as well as commercially available analogs of identified inhibitors. The precise source of test extracts or compounds is not critical to the identification of IL-12 antagonists. Accordingly, IL-12 antagonists can be identified from virtually any number of chemical extracts or compounds. Examples of such extracts or compounds that can be IL-12 antagonists include, but are not limited to, plant-, fungal-, prokaryotic- or animal-based extracts, fermentation broths, and synthetic compounds, as well as modification of existing compounds. Numerous methods are also available for generating random or directed synthesis (e.g., semi-synthesis or total synthesis) of any number of chemical compounds, including, but not limited to, saccharide-, lipid-, peptide-, and nucleic acid-based compounds. Synthetic compound libraries are commercially available from Brandon Associates (Merrimack, N.H.) and Aldrich Chemical (Milwaukee, Wis.). IL-12 antagonists can be identified from synthetic compound libraries that are commercially available from a number of companies including Maybridge Chemical Co. (Trevillet, Cornwall, UK), Comgenex (Princeton, N. J.), Brandon Associates (Merrimack, N.H.), and Microsource (New Milford, Conn.). IL-12 antagonists can be identified from a rare chemical library, such as the library that is available from Aldrich (Milwaukee, Wis.). IL-12 antagonists can be identified in libraries of natural compounds in the form of bacterial, fungal, plant, and animal extracts are commercially available from a number of sources, including Biotics (Sussex, UK), Xenova (Slough, UK), Harbor Branch Oceangraphics Institute (Ft. Pierce, Fla.), and PharmaMar, U.S.A. (Cambridge, Mass.). Natural and synthetically produced libraries and compounds are readily modified through conventional chemical, physical, and biochemical means. Useful compounds may be found within numerous chemical classes, though typically they are organic compounds, including small organic compounds. Small organic compounds have a molecular weight of more than 50 yet less than about 2,500 daltons, such as less than about 750 or less than about 350 daltons can be utilized in the methods disclosed herein. Exemplary classes include heterocycles, peptides, saccharides, steroids, and the like. The compounds may be modified to enhance efficacy, stability, pharmaceutical compatibility, and the like. In several aspects, compounds of use have a Kd for IL-12 of less than 1nM, less than 10nm, less than 1 μM, less than 10μM, or less than 1mM. Imidazopyridazine compounds have been identified as inhibitors of IL-12, see for example, U.S Patent No.10,273,237. These compounds are of use in the disclosed methods. D. IL-12 peptide variants as antagonists In one aspect, variants of an IL-12 protein which function as an antagonist can be identified by screening combinatorial libraries of mutants, such as point mutants or truncation mutants, of IL-12 to identify proteins with antagonist activity. The IL-12 protein can be a p35 or p40 variant. Thus, a library of IL-12 variants (including p35 or p40 variants) can be generated by combinatorial mutagenesis at the nucleic acid level and is encoded by a variegated gene library. A library of variants can be produced by, for example, by enzymatically ligating a mixture of synthetic oligonucleotides into gene sequences such that a degenerate set of potential sequences is expressible as individual polypeptides, or alternatively, as a set of larger fusion proteins (such as for phage display) containing the set of p35 or p40 sequences. There are a variety of methods which can be used to produce libraries of potential variants from a degenerate oligonucleotide sequence. Chemical synthesis of a degenerate gene sequence can be performed in an automatic DNA synthesizer, and the synthetic gene then ligated into an appropriate expression vector. Use of a degenerate set of genes allows for the provision, in one mixture, of all of the sequences encoding the desired set of potential antagonist sequences. Methods for synthesizing degenerate oligonucleotides are known in the art (see, for example, Narang, et al., Tetrahedron 39:3, 1983; Itakura et al. Annu. Rev. Biochem.53:323, 1984; Itakura et al. Science 198:1056, 1984). In addition, libraries of fragments of a p35 or p40 coding sequence can be used to generate a population of fragments for screening and subsequent selection of variants that are of use as an IL-12 antagonist. In one aspect, a library of coding sequence fragments can be generated by treating a double stranded PCR fragment of a coding sequence with a nuclease under conditions wherein nicking occurs only about once per molecule, denaturing the double stranded DNA, renaturing the DNA to form double stranded DNA which can include sense / antisense pairs from different nicked products, removing single stranded portions from reformed duplexes by treatment with S1 nuclease, and ligating the resulting fragment library into an expression vector. By this method, an expression library can be derived which encodes N-terminal, C-terminal and internal fragments of various sizes. Several techniques are known in the art for screening gene products of combinatorial libraries made by point mutations or truncation, and for screening cDNA libraries for gene products having a selected property. Such techniques are adaptable for rapid screening of the gene libraries generated by the combinatorial mutagenesis of IL-12. The most widely used techniques, which are amenable to high through- put analysis, for screening large gene libraries typically include cloning the gene library into replicable expression vectors, transforming appropriate cells with the resulting library of vectors, and expressing the combinatorial genes under conditions in which detection of a desired activity facilitates isolation of the vector encoding the gene whose product was detected. Recursive ensemble mutagenesis (REM) can be used in combination with the screening assays to identify PD-1 antagonists (Arkin and Youvan, Proc. Natl. Acad. Sci. USA 89:78117815, 1992; Delagrave et al., Protein Eng.6(3):327331, 1993). In one aspect, cell-based assays can be exploited to analyze a library of variants. For example, a library of expression vectors can be transfected into a cell line which ordinarily synthesizes and secretes IL- 12. The transfected cells are then cultured such that IL-12 and a particular p35 and / or p40 variant are secreted. The effect of expression of the mutant on IL-12 activity in cell supernatants can be detected, such as by any of a functional assay. Plasmid DNA can then be recovered from the cells wherein endogenous IL- 12 activity is inhibited, and the individual clones further characterized. Peptidomimetics can also be used as IL-12 antagonists. Peptide analogs are commonly used in the pharmaceutical industry as non-peptide drugs with properties analogous to those of the template peptide. These types of non-peptide compounds and are usually developed with the aid of computerized molecular modeling. Peptide mimetics that are structurally similar to therapeutically useful peptides can be used to produce an equivalent therapeutic or prophylactic effect. Generally, peptidomimetics are structurally similar to a paradigm polypeptide (for example, polypeptide that has a PD-1 biological activity) but has one or more peptide linkages optionally replaced by a --CH2NH--, --CH2S--, --CH2--CH2--, --CH.=.CH-- (cis and trans), - -COCH2--, --CH(OH)CH2--, and --CH2SO—linkages. These peptide linkages can be replaced by methods known in the art (see, for example, Morley, Trends Pharm. Sci. pp.463468, 1980; Hudson et al. Int. J. Pept. Prot. Res.14:177185, 1979; Spatola, Life Sci.38:12431249, 1986; Holladay, et al. Tetrahedron Lett. 24:44014404, 1983). Peptide mimetics can be procured economically, be stable, and can have increased half-life or absorption. Labeling of peptidomimetics usually involves covalent attachment of one or more labels, directly or through a spacer (such as by an amide group), to non-interfering position(s) on the peptidomimetic that are predicted by quantitative structure-activity data and / or molecular modeling. Such non-interfering positions generally are positions that do not form direct contacts with the macromolecules(s) to which the peptidomimetic binds to produce the therapeutic effect. Derivatization of peptidomimetics should not substantially interfere with the desired biological or pharmacological activity of the peptidomimetic. A dominant negative protein or a nucleic acid encoding a dominant negative protein that interferes with the biological activity of IL-12 can also be used in the methods disclosed herein. A dominant negative protein is any amino acid molecule having a sequence that has at least 50%, 70%, 80%, 90%, 95%, or even 99% sequence identity to at least 10, 20, 35, 50, 100, or more than 150 amino acids of the wild type protein, such as p35 or p40, to which the dominant negative protein corresponds. The dominant negative protein may be administered as by incorporating a nucleic acid molecule encoding the dominant negative protein in an expression vector. The expression vector may be a non-viral vector or a viral vector (e.g., retrovirus, recombinant adeno-associated virus, or a recombinant adenoviral vector). Alternatively, the dominant negative protein may be directly administered as a recombinant protein systemically or to the infected area using, for example, microinjection techniques. Polypeptide antagonists can be produced in prokaryotic or eukaryotic host cells by expression of polynucleotides encoding the amino acid sequence, frequently as part of a larger polypeptide (a fusion protein, such as with ras or an enzyme). Alternatively, such peptides can be synthesized by chemical methods. Methods for expression of heterologous proteins in recombinant hosts, chemical synthesis of polypeptides, and in vitro translation are well known in the art (see Maniatis et al. Molecular Cloning: A Laboratory Manual (1989), 2nd Ed., Cold Spring Harbor, N.Y.; Berger and Kimmel, Methods in Enzymology, Volume 152, Guide to Molecular Cloning Techniques (1987), Academic Press, Inc., San Diego, Calif.; Kaiser et al., Science 243:187, 1989; Merrifield, Science 232:342, 1986; Kent, Annu. Rev. Biochem.57:957, 1988). Peptides can be produced, such as by direct chemical synthesis, and used as antagonists of an IL-12 interaction with the receptor. Peptides can be produced as modified peptides, with nonpeptide moieties attached by covalent linkage to the N-terminus and / or C-terminus. In certain preferred aspects, either the carboxy-terminus or the amino-terminus, or both, are chemically modified. The most common modifications of the terminal amino and carboxyl groups are acetylation and amidation, respectively. Amino-terminal modifications such as acylation (for example, acetylation) or alkylation (for example, methylation) and carboxy-terminal-modifications such as amidation, as well as other terminal modifications, including cyclization, can be incorporated into various aspects. Certain amino-terminal and / or carboxy- terminal modifications and / or peptide extensions to the core sequence can provide advantageous physical, chemical, biochemical, and pharmacological properties, such as: enhanced stability, increased potency and / or efficacy, resistance to serum proteases, desirable pharmacokinetic properties, and others. Treatment of Subjects The disclosed methods can include treating a selected subject that has an autoimmune disease with a therapeutically effective amount of an IL-12 antagonist. Subjects with a variety of autoimmune disorders can be selected for treatment using the disclosed methods. The subject can have a systemic autoimmune disease. In some aspects, the autoimmune disease is a rheumatoid disease. In other aspects, the autoimmune disorder affects or primarily affects the joints, skin, the respiratory system, the reproductive system, the cardiovascular system, or the nervous system. In some aspects, the subject can have alopecia areata, ankylosing spondylitis, anti-phospholipid antibody syndrome, autoimmune hepatitis, Celiac disease, Crohn’s disease, Goodpasture’s Syndrome, Grave’s disease, Hashimoto’s thyroiditis, immune thrombocytopenia, IgA Nephropathy, inflammatory bowel disease (IBD), multiple sclerosis, myasthenia gravis, pemphigoid, pemphigus, polyglandular autoimmune syndrome type 2, psoriasis, psoriatic arthritis, rheumatoid arthritis, scleroderma, Sjogren’s syndrome, systemic lupus erythematosus, Takayasu’s arteriosus, type 1 diabetes, ulcerative colitis, or undifferentiated connective tissue disease (UCTD). In more aspects, the autoimmune disease is systemic lupus erythematosus (SLE). In further aspects, the subject that has SLE also has nephritis and / or skin disease. In more aspects, the subject has Sjogren’s syndrome. The selected subject can be a human subject or a veterinary subject. The selected subject can be a mammal. While the disclosed methods will typically be used to treat human subjects, they may also be used to treat similar or identical diseases in other vertebrates, such as other primates, dogs, cats, horses, and cows. Following selection of the subject, administration to the subject can be systemic or local. Examples of methods for administering the composition into mammals include, but are not limited to, oral, subcutaneous, intramuscular, intradermal, intraperitoneal, and intravenous administration. However, other routes, such as inhalation and rectal administration are contemplated. In some aspects, the method includes administering to the selected subject a therapeutically effect amount of an additional therapeutic agent. In non-limiting examples, the subject has SLE, and the method includes administering to the subject an effective amount of Belimumab, Anifrolumab or Rituximab. In other non-limiting examples, the method includes administering to the subject an effective amount of interferon (IFN)γ antagonist. The IFNγ antagonist can be an antibody that specifically binds IFNγ, such as, but not limited to, Emapalumab. In some aspects, the compositions and methods disclosed herein can be used to treat SLE in a selected subject. Treatment can include the use of the IL-12 antagonist, in addition to one or more additional agents, such as tacrolimus, disease-modifying antirheumatic drugs (DMARDs, such as corticosteroids; antimalarials, for example, hydroxychloroquine and immunosuppressants, such as methotrexate and azathioprine; hydroxychloroquine; cyclophosphamide; and mycophenolic acid), immunosuppressive drugs, intravenous immunoglobulins (IVIGs), lifestyle changes (such as avoiding sunlight and activities that induce fatigue), kidney transplantation (such as to treat lupus nephritis), and anticoagulants (such as for antiphospholipid syndrome). The amount of IL-12 antagonist used for treatment will depend upon the type of antagonist, the severity of the condition, the route of administration, the reactivity of the IL-12 antagonist with IL-12 or the activity of the IL-12, and ultimately will be decided by the treatment provider. In practicing the methods of treatment, a therapeutically effective amount of an IL-12 antagonist is administered. Generally, the amount administered provides a meaningful benefit (e.g., curing, ameliorating, delaying or preventing onset of, preventing recurrence or relapse of the autoimmune disease). One common technique to determine a therapeutically effective amount for a given patient is to administer escalating doses periodically until a meaningful benefit is observed by the treatment provider. In some non-limiting examples, when an antibody is used, a therapeutically effective dose can be in the range of about 0.05 mg / kg to about 25 mg / kg. The number of administrations may vary, depending on the individual patient and the severity of the rheumatic disease. In some aspects, treatment of the autoimmune disease is affected by administering an effective amount or dosage of a composition that total, on average, a range from at least about 0.01 to 500 milligrams of an antagonist, such as an antibody, per kilogram of patient per dose, such as from at least about 0.1 to 100 milligrams / kilogram of patient per single or multiple administration, depending upon the specific activity of the active agent contained in the composition. Alternatively, the effective serum concentration can comprise 0.1-5000 μg / ml serum concentration per single or multiple administrations. Suitable dosages are known to medical practitioners and will, of course, depend upon the particular disease state, specific activity of the composition being administered, and the particular patient undergoing treatment. In some instances, to achieve the desired therapeutic amount, it can be necessary to provide repeated administration of a particular monitored or metered dose, where the individual administrations are repeated until the desired daily dose or effect is achieved. In aspects, doses can optionally include 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 and / or 100-500 mg / kg / administration, or any range, value or fraction thereof, or to achieve a serum concentration of 0.1, 0.5, 0.9, 1.0, 1.1, 1.2, 1.5, 1.9, 2.0, 2.5, 2.9, 3.0, 3.5, 3.9, 4.0, 4.5, 4.9, 5.0, 5.5, 5.9, 6.0, 6.5, 6.9, 7.0, 7.5, 7.9, 8.0, 8.5, 8.9, 9.0, 9.5, 9.9, 10, 10.5, 10.9, 11, 11.5, 11.9, 20, 12.5, 12.9, 13.0, 13.5, 13.9, 14.0, 14.5, 4.9, 5.0, 5.5., 5.9, 6.0, 6.5, 6.9, 7.0, 7.5, 7.9, 8.0, 8.5, 8.9, 9.0, 9.5, 9.9, 10, 10.5, 10.9, 11, 11.5, 11.9, 12, 12.5, 12.9, 13.0, 13.5, 13.9, 14, 14.5, 15, 15.5, 15.9, 16, 16.5, 16.9, 17, 17.5, 17.9, 18, 18.5, 18.9, 19, 19.5, 19.9, 20, 20.5, 20.9, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 96, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1500, 2000, 2500, 3000, 3500, 4000, 4500, and / or 5000 μg / ml serum concentration per single or multiple administration, or any range, value or fraction thereof. Alternatively, the dosage administered can vary depending upon known factors, such as the pharmacodynamic characteristics of the particular agent, and its mode and route of administration; age, health, and weight of the recipient; nature and extent of symptoms, kind of concurrent treatment, frequency of treatment, and the effect desired. Usually, a dosage of active ingredient can be about 0.1 to 100 milligrams per kilogram of body weight. Ordinarily 0.1 to 50, and, preferably, 0.1 to 10 milligrams per kilogram per administration or in sustained release form is effective to obtain desired results. The composition can be administered once but may be applied periodically until either a therapeutic result is achieved or until side effects warrant discontinuation of therapy. In one example, a dose is infused over time. In one example, a continuous infusion is administered for about one to about ten days, such as for about two to five days, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 days. In another example, a dose of an agent is administered as a bolus one or more times. The selected subject can be treated at regular intervals, such as daily, biweekly, weekly, bi-monthly, or monthly, until a desired therapeutic result is achieved. Generally, the dose is sufficient to treat or ameliorate symptoms or signs of disease without producing unacceptable toxicity to the patient. Amounts effective for this use will depend upon the activity of the agent, the severity of the disease and the general state of the patient's health. An effective amount provides either subjective relief of a symptom(s) or an objectively identifiable improvement as noted by the clinician or other qualified observer. Combinations of agents are also envisioned. Administration may begin whenever the suppression or prevention of disease is desired, for example, at a certain age of a subject, or at specific time intervals. For treatment of a selected subject, depending on activity of the agent, manner of administration, nature and severity of the disorder, age and body weight of the patient, different doses are necessary. Under certain circumstances, however, higher or lower doses may be appropriate. The administration of the dose can be carried out both by single administration in the form of an individual dose unit or else several smaller dose units and also by multiple administrations of subdivided doses at specific intervals. A skilled clinician can readily determine an effective dose. As a non-limiting example, treatment of humans or animals can be provided as a one-time or periodic dosage of 0.1 to 100 mg / kg, such as 0.5, 0.9, 1.0, 1.1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 40, 45, 50, 60, 70, 80, 90 or 100 mg / kg, per day, on at least one of day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, or 40, or, alternatively or additionally, at least one of week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, or 52, or, alternatively or additionally, at least one of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 years, or any combination thereof, using single, infusion or repeated doses. Dosage forms (composition) suitable for internal administration generally contain from about 0.001 milligram to about 500 milligrams of active ingredient per unit or container. In these pharmaceutical compositions, the active ingredient will ordinarily be present in an amount of about 0.5-99.999% by weight based on the total weight of the composition. Administration of nucleic acid constructs is taught, for example, in U.S. Patent No.5,643,578; U.S. Patent No.5,593,972 and U.S. Patent No.5,817,637; and U.S. Patent No.5,880,103. The methods include liposomal delivery of the nucleic acids. One approach to administration of nucleic acids is direct administration of plasmid DNA, such as with a mammalian expression plasmid. As described above, the nucleotide sequence encoding a polypeptide can be placed under the control of a promoter to increase expression of the molecule. A CRISPR / Cas system is also of use in the methods disclosed herein. The inhibitory nucleic acid molecule can also be expressed by attenuated viral hosts or vectors or bacterial vectors. Recombinant vaccinia virus, adeno-associated virus (AAV), herpes virus, retrovirus, or other viral vectors can be used to express the peptide or protein. For example, vaccinia vectors and methods of administration are described in U.S. Patent No.4,722,848. BCG (Bacillus Calmette Guerin) provides another vector for expression of the peptides (see Stover, Nature 351:456-460, 1991). When a viral vector is utilized, it can be desirable to provide the recipient with a dosage of each recombinant virus in the composition of at least 105, at least 106, or at least 107plaque forming units / mg mammal, such as about 105to about 1010plaque forming units / mg mammal, although a lower or higher dose can be administered. The composition of recombinant viral vectors can be introduced into a subject. Generally, the quantity of recombinant viral vector to be administered is based on the titer of virus particles. An exemplary range of the virus to be administered is 105to 1010virus particles per mammal, such as a human. In some aspects, effective amount of an antibody that specifically binds IL-12 or antigen binding fragment thereof is administered to the selected subject. Antagonistic antibodies and antigen binding fragments thereof can be provided in lyophilized form and rehydrated with sterile water before administration, although they are also provided in sterile solutions of known concentration. The antibody solution is then added to an infusion bag containing 0.9% Sodium Chloride, USP, and typically administered at a dosage of from 0.5 to 15 mg / kg of body weight. Considerable experience is available in the art in the administration of antibody drugs, which have been marketed in the U.S. since the approval of RITUXAN® in 1997. Antibody drugs can be administered by slow infusion, rather than in an IV push or bolus. In one example, a higher loading dose is administered, with subsequent, maintenance doses being administered at a lower level. For example, an initial loading dose of at least 0.5 mg / kg, such as at least 1 mg / kg, such as 4 mg / kg may be infused over a period of some 90 minutes, followed by weekly maintenance doses for 4-8 weeks of at least 0.5 mg / kg, such as at least 1 mg / kg, such as 2 mg / kg infused over a 30-minute period if the previous dose was well tolerated. In one specific, non-limiting example, a pharmaceutical composition for intravenous administration includes about 0.1 µg to 10 mg of an antagonist antibody, or antigen binding fragment thereof, per patient per day. Dosages from 0.1 up to about 100 mg per subject per day can be used, particularly if the antagonistic antibody or antigen binding fragment thereof is administered to a body cavity or into a lumen of an organ. For parenteral administration, an active agent, such as, but not limited to, an antibody, can be formulated as a solution, suspension, emulsion, particle, powder, or lyophilized powder in association, or separately provided, with a pharmaceutically acceptable parenteral vehicle. Examples of such vehicles are water, saline, Ringer's solution, dextrose solution, and 1-10% human serum albumin. Liposomes and nonaqueous vehicles, such as fixed oils, can also be used. The vehicle or lyophilized powder can contain additives that maintain isotonicity (e.g., sodium chloride, mannitol) and chemical stability (e.g., buffers and preservatives). The formulation is sterilized by known or suitable techniques. Pharmaceutical compositions can be prepared and administered in dose units. Solid dose units are tablets, capsules, single injectables and even suppositories. A suitable administration format may best be determined by a medical practitioner for each subject individually. Various pharmaceutically acceptable carriers and their formulation are described in standard formulation treatises, e.g., Remington’s Pharmaceutical Sciences by E. W. Martin. See also Wang, Y. J. and Hanson, M. A., Journal of Parenteral Science and Technology, Technical Report No.10, Supp.42: 2S, 1988. The dosage form of the pharmaceutical composition will be determined by the mode of administration chosen. Suitable solid or liquid pharmaceutical preparation forms are, for example, granules, powders, tablets, coated tablets, (micro)capsules, suppositories, syrups, emulsions, suspensions, creams, aerosols, drops or injectable solution in ampoule form and also preparations with protracted release of active compounds, in whose preparation excipients and additives and / or auxiliaries such as disintegrants, binders, coating agents, swelling agents, lubricants, flavorings, sweeteners, solubilizers or scaffolds are customarily used as described above. The pharmaceutical compositions are suitable for use in a variety of drug delivery systems. For a brief review of present methods for drug delivery, see Langer, Science 249:1527-1533, 1990. Formulations for parenteral administration can contain as common excipients sterile water or saline, polyalkylene glycols, such as polyethylene glycol, oils of vegetable origin, hydrogenated naphthalenes and the like. Aqueous or oily suspensions for injection can be prepared by using an appropriate emulsifier or humidifier and a suspending agent, according to known methods. Agents for injection can be a non-toxic, non-orally administrable diluting agent, such as aqueous solution, a sterile injectable solution or suspension in a solvent. As the usable vehicle or solvent, water, Ringer's solution, isotonic saline, etc. are allowed; as an ordinary solvent or suspending solvent, sterile involatile oil can be used. For these purposes, any kind of involatile oil and fatty acid can be used, including natural or synthetic or semisynthetic fatty oils or fatty acids; natural or synthetic or semi-synthetic mono- or di- or tri-glycerides. Parental administration is known in the art and includes, but is not limited to, conventional means of injections, a gas pressured needle-less injection device as described in U.S. Pat. No.5,851,198, and a laser perforator device as described in U.S. Pat. No.5,839,446. The disclosure further relates to the administration of an IL-12 antagonist to a selected subject by parenteral, subcutaneous, intramuscular, intravenous, intrarticular, intrabronchial, intraabdominal, intracapsular, intracartilaginous, intracavitary, intracelial, intracerebellar, intracerebroventricular, intracolic, intracervical, intragastric, intrahepatic, intramyocardial, intraosteal, intrapelvic, intrapericardiac, intraperitoneal, intrapleural, intraprostatic, intrapulmonary, intrarectal, intrarenal, intraretinal, intraspinal, intrasynovial, intrathoracic, intrauterine, intravesical, intralesional, bolus, vaginal, rectal, buccal, sublingual, intranasal, or transdermal means. A composition can be prepared for use for parenteral (subcutaneous, intramuscular or intravenous) or any other administration particularly in the form of liquid solutions or suspensions; for use in vaginal or rectal administration particularly in semisolid forms, such as, but not limited to, creams and suppositories; for buccal, or sublingual administration, such as, but not limited to, in the form of tablets or capsules; or intranasally, such as, but not limited to, the form of powders, nasal drops or aerosols or certain agents; or transdermally, such as not limited to a gel, ointment, lotion, suspension or patch delivery system with chemical enhancers such as dimethyl sulfoxide to either modify the skin structure or to increase the drug concentration in the transdermal patch (Junginger, et al. In “Drug Permeation Enhancement;” Hsieh, D. S., Eds., pp.59-90 (Marcel Dekker, Inc. New York 1994), or with oxidizing agents that enable the application of formulations containing proteins and peptides onto the skin (see PCT Publication No. WO 98 / 53847), or applications of electric fields to create transient transport pathways, such as electroporation, or to increase the mobility of charged drugs through the skin, such as iontophoresis, or application of ultrasound, such as sonophoresis (U.S. Pat. Nos.4,309,989 and 4,767,402) Controlled release parenteral formulations of the compositions can be made as implants, oily injections, or as particulate systems. For a broad overview of protein delivery systems see, Banga, A.J., Therapeutic Peptides and Proteins: Formulation, Processing, and Delivery Systems, Technomic Publishing Company, Inc., Lancaster, PA, (1995) incorporated herein by reference. Particulate systems include microspheres, microparticles, microcapsules, nanocapsules, nanospheres, and nanoparticles. Microcapsules contain the therapeutic protein, such as a cytotoxin or a drug, as a central core. In microspheres the therapeutic is dispersed throughout the particle. Particles, microspheres, and microcapsules smaller than about 1 µm are generally referred to as nanoparticles, nanospheres, and nanocapsules, respectively. Capillaries have a diameter of approximately 5 µm so that only nanoparticles are administered intravenously. Microparticles are typically around 100 µm in diameter and are administered subcutaneously or intramuscularly. See, e.g., Kreuter, J., Colloidal Drug Delivery Systems, J. Kreuter, ed., Marcel Dekker, Inc., New York, NY, pp.219-342, 1994; and Tice & Tabibi, Treatise on Controlled Drug Delivery, A. Kydonieus, ed., Marcel Dekker, Inc. New York, NY, pp.315-339, 1992, both of which are incorporated herein by reference. To extend the time during which the IL-12 antagonist is available, the IL-12 antagonist can be provided as an implant, an oily injection, or as a particulate system. The particulate system can be a microparticle, a microcapsule, a microsphere, a nanocapsule, or similar particle. Polymers can be used for ion-controlled release of the compositions disclosed herein. Various degradable and nondegradable polymeric matrices for use in controlled drug delivery are known in the art (Langer, Accounts Chem. Res.26:537-542, 1993). For example, the block copolymer, polaxamer 407, exists as a viscous yet mobile liquid at low temperatures but forms a semisolid gel at body temperature. It has shown to be an effective vehicle for formulation and sustained delivery of recombinant interleukin-2 and urease (Johnston et al., Pharm. Res.9:425-434, 1992; and Pec et al., J. Parent. Sci. Tech.44(2):58-65, 1990). Alternatively, hydroxyapatite has been used as a microcarrier for controlled release of proteins (Ijntema et al., Int. J. Pharm.112:215-224, 1994). In yet another aspect, liposomes are used for controlled release as well as drug targeting of the lipid-capsulated drug (Betageri et al., Liposome Drug Delivery Systems, Technomic Publishing Co., Inc., Lancaster, PA, 1993). Numerous additional systems for controlled delivery of therapeutic proteins are known. See, e.g., U.S. Patent No.5,055,303; U.S. Patent No.5,188,837; U.S. Patent No.4,235,871; U.S. Patent No.4,501,728; U.S. Patent No.4,837,028; U.S. Patent No. 4,957,735; U.S. Patent No.5,019,369; U.S. Patent No.5,055,303; U.S. Patent No.5,514,670; U.S. Patent No.5,413,797; U.S. Patent No.5,268,164; U.S. Patent No.5,004,697; U.S. Patent No.4,902,505; U.S. Patent No.5,506,206; U.S. Patent No.5,271,961; U.S. Patent No.5,254,342 and U.S. Patent No.5,534,496, each of which is incorporated herein by reference. The following examples are provided to illustrate particular features of certain aspects of the disclosure, but the scope of the claims should not be limited to those features exemplified. EXAMPLES B cell immune responses can create an extrafollicular (EF) response or initiate a germinal center (GC) response (Elsner et al., 2020, Immunity 53: 1136-1150). The EF response generates large numbers of antibody-secreting plasmablasts (PB), leading to immediate effector function; it likely creates a type of memory B cell but may not create long-lived plasma cells (Weisel et al., 2017, Annu Rev Immunol 35: 255- 284; Liu et al., 2022, Nat Immunol 23: 1564-1576; Trivedi et al., 2019, Immunity 51: 1088-1101). Even though isotype switch and V region somatic hypermutation can occur at EF sites (Trivedi et al., 2019, Immunity 51: 1088-1101; William et al., 2002, Science 297: 2066-2070; Di Niro et al., 2015, Immunity 43: 120-131), owing to their typically short duration, EF responses do not efficiently create higher affinity progeny. In contrast, the GC response, once at peak, does not further expand nor generate much immediate effector function, but rather is specialized to select and diversify the B cell response, eventually creating diverse and higher affinity memory B cells and long-lived plasma cells (Vaidehi et al., 2022, Front Immunol 13: 898078; Victoria et al., 2022, Annu Rev Immunol 40: 413-442).Thus, each response is suited to different biological contexts. EF responses are often associated with acute or more severe infections (Cunningham et al., 2007, J Immunol 178: 6200-6207; Kaneko et al, 2020, Cell 183: 143-157; Racine et al., 2010, J Immunol 184: 5085-5093; Elsner et al., 2015, PloS Pathog 11: e1004976; Hastey et al., 2012, J Immunol 188: 5612- 5622) as well as systemic autoimmunity (William et al., 2002, Science 297: 2066-2070; Jacobson et al., 1995, Immunity 3: 509-519; Sang et al., 2014, J Immunol 193: 1609-1621), in both mice and humans (Jenks et al., 2018, Immunity 49: 725-739; Jenks et al., 2019, Immunol Rev 288: 136-148). GC responses are observed after vaccination and less severe viral infections (Elsner et al., 2020, Immunity 53: 1136-1150; Victoria et al., 2022, Annu Rev Immunol 40: 413-442; Hoehn et al., 2021, J Immunol 206: 2785-2790). In some infection models, including Salmonella enterica serovar Typhimurium (STm) infection of mice, when an unrelated immunization is administered concurrently, that EF response is enhanced and GC are dominantly suppressed by the host environment (Elsner et al., 2019, Cell Rep 29: 2796-2809). This implies host factors can regulate the relative dominance of each response type. Despite the recognition of these two modes of humoral response, the signals that control which of these divergent pathways is taken are largely unknown (Elsner et al., 2020, Immunity 53: 1136-1150). Beyond that, how such signals might work has not been well-elucidated. Gaining insight into these mechanisms could inform vaccine design and monitoring, enabling us to direct responses in one way or another depending on the need (Baumgarth et al., 2013, Immunol et al., 255: 82-94; Cirelli et al., 2017, Curr Opin Immunol 47: 64-69; Lee et al., 2022, Immunol Lett 241: 1-14; Schijns et al., 2020. Immunol Rev 296: 169-190), as well as to predict the longevity of different facets of protective humoral immunity (Weisel et al., 2017, Annu Rev Immunol 35: 255-284; Cancro et al., 2021, Immunol Rev 303: 72-82). Understanding the control of humoral response pathways could be important for developing therapies to autoimmune diseases, and also for understanding immunopathology of acute infections, such as with SARS-CoV2, that feature dominant EF responses (Kaneko et al., 2020, Cell 183: 143-157; Woodruff et al., 2020, Nat Immunol 21: 1506-1516; Pillai et al., 2022, Clin Lab Med 42: 75-84). IL-12 diverts T cells away from TFH and towards TH1, thus short-circuiting the TFH-dependent GC response (Elsner et al., 2019, Cell Rep 29: 2796-2809). In these T cell-focused studies there were also clues that IL-12 could have important and direct effects on B cells. Giving exogenous IL-12 has been reported to promote antibody secreting cells in vivo, but neither the mechanism, nor whether this effect acts directly on B cells was addressed (Kim et al., 2008, J Exp Med 205: 2437-2448; Dubois et al., 1998, J Immunol 161: 2223-2231). IL-12 can be secreted by both human (Durali et al., 2003, Blood 102: 4084-4089) and mouse B cells (Liu et al., 2003, Nat Immunol 4: 687-693; Harris et al., 2000, Nat Immunol 1: 475-482). Some studies also showed that B cells express the IL-12 receptor (Vogel et al., 1996, Int Immunol 8: 1955-1962; Airoldi et al., 2000, J Immunol 165: 6880-6888) and can secrete IFNγ in response to IL-12 (Durali et al., 2003, Blood 102: 4084-4089; Liu et al., 2003, Nat Immunol 4: 687-693; Airoldi et al., 2000, J Immunol 165: 6880-6888; Szabo et al., 2000, Cell 100: 655-669). In T cells, IL-12 induces IFNγ, initiating and sustaining TH1 differentiation (Szabo et al., 2000, Cell 100: 655-669; Schulz et al., 2009, Immunity 30: 673-683; Afkarian et al., 2002, Nat Immunol 3: 549-557; Hsieh et al., 1993, Science 260: 547-549; Seder et al., 1993, PNAS 90: 10188-10192). However, prior studies on B cells have left open the biologic roles of IL-12 in cross-regulation of IFNγ, the direct effects of IL-12 in promoting proliferation and PB differentiation, and in particular the B cell-autonomous roles of IL-12 and IFNγ both in vivo and in vitro. Further, while Harris et al provided seminal data on the concept that B cell cytokine secretion and polarization could influence T cell differentiation (Harris et al., 2000, Nat Immunol 1: 475-482; Lund et al., 2010, Nat Rev Immunol 10: 236- 247), the role of B cell-derived IL-12 in T cell polarization in vivo was not explored. Here a combination of genetic tools, in vitro cultures, and in vivo cell transfers were used to dissect the roles of IL-12 and IFNγ in regulating B cell differentiation both in vitro and in vivo, as well as to assess the role of B cell-derived IL-12 on T cell differentiation during an in vivo immune response. IL-12 skews B cells toward PB and away from GC by inducing a B cell intrinsic feed-forward loop that amplifies IFNγ production, which then directly promotes PB differentiation. In addition to IL-12 promoting IFNγ production, the combination of lower doses of IL-12 and IFNγ leads to unique biological responses and gene expression patterns. In vivo, B cells lacking both cytokine receptors produce fewer PB than cells lacking either individually, directly demonstrating the synthetic interactions between the two cytokines in a B cell- intrinsic fashion. B cell production of IL-12 also regulates T cell differentiation in vivo, producing a coordinated and self-reinforcing shift toward TH1 / PB at the expense of TFH / GC development. Hence, this study uncovers the roles of IL-12 and IFNγ in a B cell-autonomous feedforward regulatory circuit that enhances B cell proliferation and PB differentiation, and further elucidate the mechanisms by which it operates. EXAMPLE 1: MATERIALS AND METHODS Mice C57BL / 6 (B6) (stock #000664,), CD45.1 B6 (stock #002014; B6.SJL-PtprcaPepcb / BoyJ), IFN- gamma receptor 1 KO B6 mice (stock #003288; B6.129S7-Ifngr1tm1Agt / J), STAT4 KO B6 (stock #028526; C57BL / 6J-Stat4em3Adiui / J), IL12p40 KO B6 (stock #002693; B6.129S1-Il12btm1Jm / J), T-bet-flox (stock #022741; B6.129-Tbx21tm2Srnr / J ) were purchased from Jackson Laboratories. B1-8+ / -62x Vk8R+ / - CD45.1 / 2 C57BL / 6 mice, containing very low frequencies of NP-specific B cells and little to no STm specific B cells were used for BM chimera hosts. For mixed cell transfer recipients, OTII+ / - Rag2KO CD45.1 / 2 mice were generated by crossing OTII Tg from Taconic Rag2 KO B6 background (stock #1896; B6.129S6-Rag2tm1FwaTg(TcraTcrb)425Cbn) to Jax Rag2KO B6 (stock #008449; B6.Cg-Rag2tm1.1Cgn / J) and to generate OTII Tg (Taconic) Rag2 KO (Jax) B6 and then crossed to CD45.1 Rag2 KO B6 to generate OTII Tg Rag2 KO CD45.1 / 2 B6 recipients. CD19-Cre B6 (Jax #006785 B6.129P2(C)-Cd19tm1(cre)Cgn / J), IL12Rb2 KO B6 (Jax #003248 B6.129S1-Il12rb2tm1Jm / J), IFNγ KO B6 (Jax #002287; B6.129S7-Ifngtm1Ts / J), and IFNγR-flox B6 (Jax #025394; C57BL / 6N-Ifngr1tm1.1Rds / J) mice were gifts. Mice were bred and housed in specific pathogen free conditions and all experiments were conducted under protocols approved by the University of Pittsburgh Institutional Animal Care and Use Committee (IACUC). All mice were between the age of 8-16 weeks at the start of experiments, except BM donors, which were between 5-8 weeks. For direct infections and immunizations, males and females were both used and distributed evenly among groups. For BM chimeras, donor cells were from females, transferred into both males and females; no sex-based differences were observed in any experiment. For adoptive cell transfers one experiment was performed with all male and the other with all female donors and recipients and the results were pooled. For all experiments using CD19-Cre x IFNγ-flox or x T-bet-flox mice, Cre- negative littermate controls were co-housed with Cre+ experimental mice of the same sex prior to and throughout the experiment. Bacterial strains Salmonella enterica serovar Typhimurium (STm) aroA attenuated strain SL326163, provided by Roy Curtiss III, Arizona State University) was used for all experiments. Glycerol stocks were prepared by growing bacteria overnight in Luria broth, then mixed 1:1 with sterile 50% glycerol and stored at -80oC. Mixed bone marrow chimeras Procedures to generate mixed BM chimeras were previously described (Elsner et al., 2019, Cell Rep 29: 2796-2809). Briefly, recipient mice expressing an irrelevant BCR, B18+ / - Vk8R+ / - CD45.1 / 2 C57BL / 6, were exposed to 900 rads of irradiation, and then rested for 4-8 hours prior to BM cell injection. Donor cells were isolated by flushing femurs and tibias with sterile stem cell buffer (SCB: PBS with 2% fetal bovine serum (Gemini Bio Products or GE HyClone) and 1 mM EDTA), made into single cell suspension by vigorous pipetting through p1000 tips, and strained through 100 µM mesh filters. Red blood cells were lysed with ACK buffer (Gibco) for 60 seconds, washed with stem cell buffer, then washed three times with sterile PBS. Live cells were enumerated by trypan blue manual cell counting. Cells were resuspended at 25-50 million cells / mL in PBS, and equal numbers of CD45.1 cells were mixed with either IL12Rb2 KO CD45.2, IFNgR1 KO CD45.2, or IL12Rb2 KO IFNgR KO CD45.2 (double KO) cells. Mice were given a 200 µL cell suspension by tail vein injection for a total of 5-10 million BM cells per recipient. Mice were fed TMS food (Trimethroprim sulfadiazine, Evnigo) for 4 weeks, and wet TMS pellets were provided for the first week. Mice were switched to standard chow for the remaining 4-8 weeks and then infected and immunized as described. Infection and Immunization To prepare STm, one day prior to injection, stabs of frozen STm glycerol stock were inoculated into Luria broth (Fisher) containing 100 µg / mL streptomycin and grown at 37oC overnight with shaking. The day of injection, heat killed bacteria were prepared as follows: cells were pelleted cells at 1800 rcf, washed twice in PBS, resuspended in PBS, transferred to a fresh tube, and incubated at 56oC for 1 hour. For infectious inoculum, bacterial cultures were split 1:25 into fresh media and grown for an additional 2 hours at 37oC to allow bacteria to reach mid-log phase, then washed 3 times in room temperature sterile PBS. Bacterial concentration was estimated by absorbance at OD600, and 1-5x105colony forming units were injected i.p. in 200 µL PBS. Colony forming units of infectious inoculum, and absence of live bacteria in heat killed inoculum, were confirmed by overnight growth at 37oC of serial dilutions of inoculum on Luria broth agar (BD Difco) plates with streptomycin. For NP-CGG immunization, mice were immunized with 50 µg NP- CGG precipitated in alum i.p. in 200 µL PBS. The ratios of NP to CGG ranged from 31-33. Bacterial burden Whole spleens were weighed and a central portion weighing between 20 - 80 mg was placed in PBS and disrupted either by sonication, or with a Tissue-Tearor, Model 985370 (Biospec Products), to lyse splenic cells. Serial dilutions were grown on Luria broth agar plates with streptomycin overnight at 37oC to quantify the number of colony forming units, which was used to calculate the total number of bacteria per mg of splenic tissue and of the whole spleen. Flow cytometry analysis Remaining spleen pieces were weighed and made into single cell suspensions by mechanical disruption in STm media (PBS + 5% bovine serum + 2 mM EDTA). RBC were lysed with ACK lysis buffer for 60 seconds, washed and resuspended in STm media, and live cells enumerated with trypan blue on a hemacytometer. If the staining panel included anti-IFNγ, ten million cells were washed in R10 (RPMI 1640 (Gibco) + 10% FBS (Gemini Bio Products or GE HyClone) + penicillin / streptomycin (Gibco), 10 mM HEPES (Corning), and 2 mM L-glutamate (Corning)), resuspended in 100 µL R10, rested for 15 min at 37oC, then 100 µL of 0.2 µg / mL Phorbol 12-myristate 13-acetate (PMA, Sigma Millipore) + 2 µg / mL Ionomycin (Sigma Millipore) + 10 µg / mL Brefeldin A (Biolegend) was added, and the mixture incubated for 4 hours at 37oC. Cells were pelleted and washed once in PBS before staining. For all other stains, five million cells per sample were stained at 100 million cells / mL with the dead cell discriminator Ghost Violet 510 or Ghost UV450 (Tonbo, per manufacturers protocol) in PBS, and washed with staining media (SM; PBS with 3% bovine serum (Gibco), 1 mM EDTA, and 0.02% sodium azide). Cells were stained with fluorescently conjugated antibodies as labeled in figures (FIG.17) in SM for 20 min on ice, then washed twice with staining media, and fixed with 1% PFA in PBS for 20 minutes on ice. For intracellular stains, cells were instead fixed / permeabilized with FoxP3 Transcription Factor staining Kit (Invitrogen) for 30 minutes on ice. After fixation, all wash steps pelleted cells at rcf 750. Cells were washed twice with FoxP3 Kit permeabilization buffer, resuspended with 25 uL SM containing 10% mouse and 10% rat serum, and 25 uL SM containing 2x concentration of intracellular stain antibodies (CXCR5, T-bet, Bcl-6, IRF4, Blimp1, and IFNγ) was added, and the mixture incubated overnight at 4oC. Cells were then washed twice with FoxP3 Kit permeabilization buffer, resuspended in SM, and data collected using BD Biosciences LSRII or Fortessa or Cytek Aurora. All wash steps used 500 rcf to pellet cells here and for all remaining sections unless otherwise specified. Cell purification by magnetic bead depletion Single cell suspensions of splenocytes were stained at 108cells / mL in SCB with cocktails of biotinylated antibodies as listed in each section below for 15 minutes on ice, then washed twice with SCB. Cells were resuspended to 108cells / mL in SCB and 120 uL of Streptavidin Particles Plus - DM (BD Biosciences) magnetic beads were added per mL of cells. Cells were then brought up to 6 mL and negative enrichment was performed with EasySep Magnets (Stem Cell Technologies). Adoptive mixed cell transfers B cells were purified by magnetic depletion using biotinylated antibodies specific to CD4, CD8, CD11b, CD11c (FIG.17). Purity was checked by flow cytometry after staining with Ghost UV510 and anti- CD19. CD4+ T cells were enriched using biotinylated antibodies specific to CD8, CD19, CD45R, CD11b, CD11c (FIG.17). Purity was checked by flow cytometry after staining with Ghost UV510 and anti-CD4. Cells were washed with PBS twice, and resuspended in PBS to 2x108B cells / mL or 3x107CD4 T cells / mL. For injections, 100 µL of each of the desired genotype of B and T cells was mixed, and 200 µL of the cell mixture per mouse was injected into the tail vein of OTII Tg Rag2 KO CD45. OTII Tg Rag2 KO hosts were chosen for hosts because they have better splenic architecture than Rag2 KO mice, but the host T cells are of irrelevant specificity. In vitro murine B cell culture B cells were enriched by magnetic depletion using biotinylated antibodies specific to CD4, CD8, CD11b, CD11c, CD49b, GR1, CD138, F4 / 80, Ter119, TCRb, and NK1.1 (FIG.17). Purity was checked by flow cytometry after staining with Ghost UV510 and either anti-CD19 or anti-CD45R. After enrichment, cells were labeled with violet proliferation dye (BD Biosciences) as follows: cells were washed once in PBS, resuspended in 1 mL cold PBS and warmed to 37oC for 10 min. Then 1 mL of 37oC 2x dye in PBS was added to the cells for a final concentration of 1 mM. Cells were gently inverted to mix, and incubated at 37oC for 10 min, then quenched with cold SCB. Cells were then pelleted and washed once in R10 and resuspended to 5x106cells / mL in R10. Cells were warmed at 37oC for approximately 30 minutes. All blocking antibodies (FIG.17) were used at a final concentration of 10 µg / mL, and the cytokines IL-12 (Peprotech) and IFNγ (Peprotech) were used at concentrations as indicated in figures. Each cytokine or blocking antibody was diluted to 8x final concentration and 25 µL was added per culture well, then 50 µL of 4x LPS was added (final concentration 5 µg / mL), finally 100 µL of cells was added per well, ending with 200 µL total volume per well in 96 well round bottom plates. In some experiments, CpG ON1826 (final concentration 10 µg / mL) was used as the TLR-agonist instead of LPS. Cells were cultured at 37oC for 4 days before staining. Cells were washed with PBS and stained as described above with Ghost UV450, then washed and surface stained for CD138 and CD45R, washed and intracellularly-stained using the FoxP3 Fix / Perm kit and antibodies to Blimp-1, T-bet, and IRF4 as described above. In vitro human B cell culture Lymphocytes were acquired from spleens of human organ donors as previously described, an IRB was not necessary as isolation of tissues from organ donors does not qualify as human subjects research, as confirmed by the Columbia University internal review board62. For all wash steps cells were pelleted for 7 min at 500g. Cells were thawed into 37oC R10, and maintained at 37oC through CFSE labeling. Cells were washed once with PBS, resuspended in PBS and an equal volume of 2 µM CFSE in PBS was added, gently mixed, incubated for 10 min and quenched with cold SCB. Cells were washed once more with SCB and B cells were enriched by magnetic depletion using biotinylated antibodies to CD2, CD3, CD14, CD16, and CD36 (Supplementary Table 1) and placed into cell culture following the same methods described above for mouse B cells. Purity was checked using flow cytometry after staining for GhostUV50, anti-CD19 and anti- CD38, and was typically 93-97%. Cells were cultured at either 3.75, 7.5, or 15 x 104cells (as indicated in each figure) per well in 96 well round bottom plates, depending on how many cells were obtained. Cells were stimulated with CpG ODN2006 (1 µg / mL), recombinant human IL-12 (20 ng / mL, Peprotech), recombinant human IFNγ (100 ng / mL, Peprotech), and IL-12 and IFNγ neutralizing antibodies (10 µg / mL, both BioXCell), clones 20C2 and B133.5 respectively. For %PB, optimal cell concentrations were the following for donors 1-7 respectively: (7.5, 7.5, 15, 3.75, 3.75, 7.5, 3.75) x 104cells per well. Cytokine quantification Serum was obtained from blood coagulated at room temperature for 30 minutes, pelleted at 10,000 rcf for 5 minutes and stored at -30oC. Culture supernatants were stored at -80oC. IL-12 and IFNγ were quantified in culture supernatants or serum using LegendPlex Mouse B cell Panel Mix and Match Subpanel kit (BioLegend), following the manufacturer instructions. Cytokine detection was quantified using Biolegend Legendplex Qognit software (version 2023). ELISPOT ACK-lysed single cell suspensions were resuspended in B cell media (RPMI with 10% fetal plex serum (Gemini Bio Products), penicillin / streptomycin (Gibco), 25 ug / mL gentamycin (Thermo Fisher), and L-glutamate (Corning)). Immulon 4-HBX plates were coated with NP4-BSA or NP16-BSA at 5 µg / mL, or with anti-mouse kappa 1 µg / mL + anti-mouse lambda 1µg / mL in PBS. Non-specific binding was blocked by incubating with 1% bovine serum albumin (Gemini Bio Products) in PBS for 1 hour. Cells were plated at 5x105cells / well for NP-specific and total IgG spots, and at 5x104cells / well for total IgM spots, with 3x serial dilutions down the plate, then incubated at 37oC overnight. Spots were detected using alkaline phosphatase conjugated antibodies to IgM, IgG1, IgG2b, or IgG2c at 1 / 2000 dilution (FIG.17). Spots were revealed with 0.55 µg / mL 5-bromo-4-chloro-3-indolyl-phosphate (BCIP) in Tris / NaCl solution (100 mM Tris base, 100 mM NaCl, 5 mM MgCl26 H2O, pH 9.5) with 0.5% Low Melt Agarose (American Bioanalytical). Spots were counted under a light microscope the following day. Bulk RNA sequencing Cells were prepared for culture as describe above from 3 individual mice. After 4 or 24 hours of culture, cells were washed once in PBS, and resuspended in Qiagen RNeasy Plus Micro Kit buffer RLT with 20 µL beta-mercaptoethanol (Sigma) per mL RLT, and stored at -80oC. RNA was isolated according to the manufacturer’s protocol. cDNA was generated from 8.5 µL RNA using the Takara Smart-Seq HT kit (Takara, 634438). All samples passed quality control with full-length cDNA and proceeded to library preparation using an Illumina Nextera FLEX Kit (Illumina, 20018705) with UDI indexes (Illumina, 20027214) added using 12 PCR cycles. Libraries were pooled and sequenced using Illumina NextSeq 500 with 75 bp paired-end reads and aligned to the mm10 genome using the STAR aligner (Dobin et al., 2013, Bioinformatics 29: 15-21). Gene-level counts were determined using featureCounts (Liao et al., 2014, Bioinformatics 30: 923-930), and raw counts were quantile normalized to each other for differential expression using the voom method (Law et al., 2014, Genome Biol 15: R29) in the Limma (version 3.52.2) R package (Ritchie et al., 2015, Nucleic Acids Res 43:e47). For normalization of the datasets, the Quantile method was used. All gene-set enrichment analysis (GSEA) were performed using the rankSumTestWithCorrelation function in limma, which explicitly corrects for correlation among genes in the gene set being interrogated. Heatmap, bar plots and X-Y plots were built using ggplot2 (version 3.2.1) in R (version 3.6.1). Quantification, Statistical Analysis, Software Statistical significance was quantified with GraphPad Prism software by two-tailed Student’s t test or one-way ANOVA as indicated in each figure. A P-value <= 0.05 was considered significant, with the following symbols used to denote P-value ranges: P < =0.05(*), P < 0.01 (**), P < 0.001 (***), P < 0.0001 (****). For mixed BM chimera “fold-advantage” calculations, the sample group was compared to the hypothetical mean of no advantage equaling using a one-sample t test. A P-value P <= 0.0332 was considered significant, with the following symbols used to denote P-value ranges: P < 0.0332(*), P < 0.0021 (**), P < 0.0002 (***), P < 0.0001 (****). Cell number was calculated per spleen using a combination of FACS analysis and trypan blue live cell counts as follows: the percent of cell of interest among live cells was determined by FACS, then the ratio of spleen processed for FACS analysis by weight as a portion of the total weight was used to calculate the total number of cells of interest per spleen. All flow cytometry data was analyzed using FlowJo version 10 (BD), and figures prepared using Inkscape version 1.0.2. EXAMPLE 2: IL-12 signaling on either B cells or CD4 T cells is sufficient to suppress GC To address how IL-12 acts to suppress GC reactions, IL-12R deficient (IL12Rb2 - / -) B6 mice were infected with STm i.p.3 days prior to i.p. immunization with the hapten NP-CGG (nitrophenyl-Chicken Gamma Globulin) and assessed GC B cells in the spleens 12 days later. Control mice received heat killed Salmonella (HK Ctl), which does not suppress GC reactions. In WT mice, NP-specific GC B cell development was suppressed by STm infection, compared to HK controls, but frequencies and numbers of NP-specific GC B cells were restored in IL-12R KO mice (FIGs.1A-1B; FIGs.2A-2B). IL-12 is crucial for host defense to STm infection (Lehmann et al., 2001, J Immunol 167: 5304-5315), and as expected, infected IL12Rb2 - / - mice had higher bacterial burdens (FIG.1C), yet GC were restored, even in the presence of higher bacterial burden. To determine whether IL-12 signaling on either CD4 T cells or B cells alone is sufficient to suppress GC formation, reciprocal cell transfer experiments were performed using IL-12R KO B and T cells (FIG. 1D). One day after cell injections, mice were immunized i.p. with NP-CGG then 3-4 hours later HK or infectious STm was also injected i.p. As NP-specific B cells were rare, total GC B cell frequencies and numbers were measured at day 12 (FIGs.2C-2D). Recapitulating the direct infection system, STm infection suppressed GC in WT T + WT B recipients compared to HK controls, but infection did not suppress GC in KO T + KO B recipients (FIGs.1E-1F). Notably, expression of IL-12R on either B cells or T cells alone, in an otherwise IL-12R intact host, was sufficient to suppress GC (FIGs.1E-1F). EXAMPLE 3: B cell-intrinsic IL-12 signaling is necessary and sufficient to promote PB differentiation Recombinant IL-12 injection suppresses GC formation but promotes PB generation (Elsner et al., 2019, Cell Rep 29, 2796-2809). To test whether IL-12 promotes PB differentiation B cell-intrinsically, mixed bone marrow (BM) chimeras were generated and reconstituted with 50% WT CD45.1 + 50% IL12Rb2 KO CD45.2 BM. After 10 weeks they were infected with STm or injected HK control, followed 3 days later by NP-CGG immunization, and B cells were examined 12 days later. FACS analysis of resting CD4 T cells showed approximately a 50:50 CD45.1 / CD45.2 ratio (=1) as expected, whereas within resting B cells CD45.2 IL-12R KO cells were over-represented at ~2-fold advantage compared to T cells (FIGs.4A- 4D), regardless of the treatment given (FIG.3B). To account for the over-represented IL-12R KO cells among resting B cells, the competitive advantage for PB was normalized to resting B cells of the same mouse (FIGs.4A-4D), as PB would have differentiated from the resting B cell compartment. Normalizing to the relative contribution of each genotype in the resting B cells from the same mouse, there was a strong competitive advantage for WT cells in PB differentiation, ranging from an average of 3.0 in mice given HK Stm to 2.0 in the infected animals (FIGs.3A-3B) indicating a B cell-intrinsic effect of IL-12R in enhancing the PB response during STm infection or with exposure to HK STm. IL-12Rb2, when paired with gp130, forms the IL-35 receptor (Tait et al., 2019, Immunity 50: 851- 870). To confirm that IL-12 is sufficient to promote PB in vivo, NP-CGG immunized WT mice were administered IL-12 at days 1, 2, and 3 post immunization and assessed for splenic PB’s at day 4, prior to GC formation. NP-specific PB were higher in rIL-12 treated vs control mice (FIG.3C). Of note, IL-12 effects can be seen as early as day 4, indicating it can act prior to GC formation. In summary, IL-12 promotes a maximal PB response by acting directly on B cells. EXAMPLE 4: IL-12 promotes both proliferation and differentiation from purified B cells in vitro To dissect whether the effect of IL-12 on PB numbers was a result of increased proliferation, differentiation or both, the effect of IL-12 on LPS-induced B cell proliferation and differentiation in vitro was assessed using IL12p40 KO B cells to exclude effects of B cell-derived IL-12 (Liu et al., 2003, Nat Immunol 4: 687-693; Harris et al., 2000, Nat Immunol 1: 475-482). IL-12 reduced the frequency of undivided cells and increased the average number of divisions, an effect observed with as little as 20 pg / ml IL-12 (FIG.5A). There were higher frequencies of PB (Blimp-1+CD138+), independent of the cellular division number (Hasbold et al., 1998, Eur J Immunol 28: 1040-1051; Hodgkin et al., 1996, J Exp Med 184: 277-281; Tangye et al., 2002, J Immunol 169: 4298-4306) when cultures contained at least 200 pg / mL IL-12 (FIG.5B; FIG.6A). While IL-12 also reduced the number of live cells at 4 days of culture, there were still more total PB in the presence of IL-12 (FIG.6B, middle and right panels). Similar results were observed using TLR9 stimulation with CpG in lieu of LPS (FIGs.6C-6E). IL-12 directly promotes both division of B cells and their differentiation into PB, with a higher concentration required for the latter. EXAMPLE 5: IL-12 induces B cell production of IFNγ that promotes PB differentiation through autocrine signaling IL-12 potentially functions by promoting IFNγ production from B cells, which in turn promotes proliferation and differentiation. To test this hypothesis, B cells were purified from WT, IL12p40 KO, IL12Rb2 KO, STAT4 KO, and IFNgR1 KO mice and cultured with LPS and increasing concentrations of IL-12 or an IL-12 blocking antibody. IL-12R, STAT4, and critically IFNgR were all necessary for IL-12 to promote PB differentiation (FIG.7A). Furthermore, WT cells produced more PB than IL12p40 KO cells (FIG.7A), indicating that autocrine IL-12 production contributes to PB differentiation. This was confirmed by comparing %PB as a function of division number for WT and IL12p40 KO cells at 200 pg / ml of added IL-12 (FIG.8A). IL-12 also enhanced the frequency of B cells co-expressing IRF4 and Blimp-1 (Nutt et al., 2015, Nat Rev Immunol 15: 160-171; Trezise et al., 2021, Immunol Rev 303: 23-34), again with WT cells generating more such cells than IL12p40 KO cells (FIG.7B). Since T-bet is essential for TH1differentiation, T-bet expression was also examined. IL-12 induced T-bet expression in B cells in a STAT4 and IFNgR dependent way, with T-bet expression primarily in Blimp-1negcells (FIG.7C). That IFNgR was required for responses implied that autocrine IFNγ is necessary for IL-12 to promote PB differentiation. To test this, B cells purified from IL12p40 KO or IFNγ KO mice were cultured with either IL-12 or IFNγ. IL-12 was not sufficient to promote PB differentiation from IFNγ KO cells, whereas IFNγ was sufficient for both IL12p40 KO and IFNγ KO cells (FIG.7D). The same was true for the ability of IL-12 and IFNγ to promote proliferation (FIGs.8B-8D) and differentiation as a function of division number (FIG.8E). These data suggest that IL-12 functions by inducing IFNγ production, which promotes PB differentiation in an autocrine fashion. EXAMPLE 6: B cell expression of IFNγ receptor contributes to PB responses during Salmonella infection To determine whether IFNγ promotes PB differentiation in vivo, d CD19Cre+ / -IFNgR1f / fmice (B- KO) or control mice (B-WT) were infected with STm or administered HK STm 3 days prior to NP-CGG immunization and assessed PB 5 days later. In STm infected mice only, IFNgR deficient B cells made decreased numbers of NP-specific IgM antibody forming cells (AFC) and strongly decreased IgG2c AFC (FIG.9A), consistent with the role of IFNγ in IgG2a / c class switch (Peng et al., 2002, PNAS 99: 5545- 5550). IgG1 and IgG2b AFC were unaffected, while the sum total of NP-specific AFC was also reduced in the spleens of STm infected B-KO mice (FIG.10A). Hence, during infection, IFNγ promotes PB differentiation in vivo by acting directly on the B cell. Furthermore, B-KO mice had slightly but significantly higher bacterial burdens (FIG.9B), possibly indicating a role for IFNγ sensing B cells in the early control of bacterial replication (Hess et al., 1996, J Immunol 156: 3321-3326). Consistent with such a B cell role, there were significantly fewer IFNγ+B cells by FACS among B-KO B cells (FIG.9C); there was no effect on IFNγ+CD4 T cells (FIG.9C and FIG.10B). Flow cytometric measurement of IFNgR expression revealed that it was important for both expansion and differentiation. The majority of resting B cells, GC B cells, and PB in WT mice expressed IFNgR. Few resting cells from B-KO mice expressed IFNgR, as expected, but deletion was less efficient among GC B cells, and PB expressed as much IFNgR as B-WT mice (FIG.9D and FIG.10C-10D), showing a strong selection for B cells that failed to delete IFNgR. The selective expansion of B cells that escaped CD19-Cre mediated deletion of IFNgR also implies that the phenotypes observed were minimal indicators of the effects of the IFNgR in B cells on PB differentiation and expansion. EXAMPLE 7: T-bet expression in B cells is not necessary for PB differentiation during Salmonella infection T-bet was induced by IL-12 in vitro. To determine whether T-bet-deficient B cells phenocopy IFNgR-deficient B cells, the above experiment was repeated using CD19Cre+ / -T-betf / fmice (T-bet B-KO) and Cre-negative T-betf / fcontrols (T-bet B-WT). Though T-bet was necessary for IgG2c AFC, T-bet deficiency had no impact on IgM AFC (FIG.9E), and it did not change the total AFC per spleen (FIG.10E). T-bet deletion also had no effect on bacterial burden or the frequencies of IFNγ-producing CD4 T cells and B cells (FIGs.9F-9G). In vivo, very few B cells expressed T-bet, even in STm infected mice; however, there was T- bet expression after IL-12 treatment in vivo among a population of non-GC B cells, confirming that IL-12 is capable of inducing T-bet in some B cells in vivo. Thus, promotion of PB differentiation by IFNγ in vivo is T-bet-independent during Stm infection. T-bet WT and T-bet KO cells were equally capable of PB differentiation in vitro under IL-12 blockade with only endogenous IFNγ available (FIG.9H). In contrast, PB differentiation was reduced in T- bet KO cells when either IL-12 or IFNγ was added alone. However, among T-bet KO cells, IL-12 was still able to induce more PB differentiation compared to control, showing that the effects of IL-12 are not entirely mediated through T-bet (FIG.9H). Blocking IFNγ eliminated the effect of IL-12 on T-bet KO B cells (FIG. 9I). Similarly, blocking IL-12 eliminated the ability of IFNγ to promote PB differentiation in T-bet KO cells. Therefore, neither IL-12 nor IFNγ is sufficient to promote PB differentiation from T-bet KO cells in vitro, whereas the combination of both IL-12 and IFNγ promote PB differentiation independently of T-bet. However, although T-bet dependent mechanisms dominate in vitro, T-bet independent and IL-12 / IFNγ cooperative pathways appear sufficient for in vivo PB generation. EXAMPLE 8: IL-12 and IFNγ synergize at low concentrations, requiring autocrine cytokine production To further explore the cooperative effects of IL-12 and IFNγ, WT or cytokine KO B cells were cultured in suboptimal concentrations of IL-12 and IFNγ. For WT B cells, compared to blocking both endogenous IL-12 and IFNγ, the addition of IL-12 at 20 pg / mL, concurrent with IFNγ blockade, was insufficient to enhance PB differentiation (FIG.11A). IFNγ added at 0.5 ng / mL along with blocking IL-12 had only a small enhancing effect on PB differentiation, primarily at the latest divisions. However, together the cytokines at these concentrations synergistically enhanced PB differentiation. Interestingly, IL12p40 KO cells did not show synergistic enhancement of adding IL-12 along with IFNγ, compared to IFNγ alone. Further, all effects of cytokine addition were abolished in IFNγ KO B cells (FIGs.11A-11B). Results from cytokine KO cells indicate that synergistic cytokine action that promotes PB differentiation requires autocrine production of both cytokines. Since IL-12 was not able to promote PB from IFNγ deficient cells (FIG.7D), presumably IL-12 acts upstream to induce IFNγ production. Proliferation, however, was not as strongly impacted at these concentrations (FIGs.11C-11D), suggesting different mechanisms or scales of regulation. EXAMPLE 9: IL-12 and IFNγ together induce unique gene expression changes While autocrine positive feedback clearly occurs, the mechanism of cytokine synergy may also involve induction of unique target gene expression only in the presence of both cytokines. To test this, the effects of IL-12 and IFNγ alone and in combination was tested on gene expression in B cells stimulated for 4 or 24hrs (FIG.13A, GEO accession GSE231931, currently accessible with reviewer token “mxmtkyksxpinxmf”). At 4hrs, IL-12 significantly upregulated transcripts of only 3 genes. Strikingly, one of these genes was IFNγ itself, whereas IFNγ did not induce its own expression (FIG.12C). At 4hrs, IFNγ modulated expression of many more genes than did IL-12 (FIG.12A). Most of the genes whose expression was increased by IFNγ alone were also upregulated by the combination of IL-12 and IFNγ (FIG.13B). Increasing doses of IFNγ induced additional genes (FIG.14B) and increased FC values for other genes, including Tbx21 (T-bet) and the Il12rb1 subunit of the IL-12R (FIG.12C). At 24 hours, only 24% (57 / 236) of IFNγ-induced differentially expressed genes (DEG) detected at 4 hours were still up at 24hrs (FIGs.12A, 12D). However, in the presence of IL-12, an additional 51 genes from the 4hr set were still significantly upregulated at 24hr (FIG.12D). These results suggest that IFNγ induces negative feedback that can be overcome by IL-12. In contrast, downregulated DEG were largely independent of timing. Only 3% (5 / 146) of IFNγ-downregulated DEG at 4hrs were also down at 24hrs. Adding IL-12 to the 24hr condition only increased the number of genes down at both 4 and 24hrs by 10% (14 / 146); whereas, 87% (90 / 103) downregulated DEG at 24 hours were unique to the IL-12+IFNγ condition (FIGs.13C-13D). Notably, IFNγ induced Socs1, Socs3, and Cish (Sobah et al., 2021, Front Med 8: 727987) (FIG. 12C), all of which negatively regulate IL-12 and / or IFNγ signaling in CD4 T cells. Mechanisms by which IL-12 could counteract the negative feedback in IFNγ-induced genes were also identified: IL-12+IFNγ induced both subunits of the IL-12R (Il12rb1, Il12rb2) and Stat4 at 24 hours, whereas IFNγ alone was not sufficient to upregulate Il12rb2 (FIGs.12C, 12E); this could serve to positively reinforce the effects of IL-12 itself over time. Indicative of the important effect of synergy between IFNγ and IL-12, at 24 hours, 66% of upregulated DEG (155 / 235) required both cytokines for induction, (FIG.12B), and, of those, 67% (104 / 155) were not upregulated DEG at 4 hours (FIG.12D), meaning that they were uniquely induced by positive feedback that evolved over time. Among the DEG upregulated only with both cytokines were Stat4 and Stat1, the STAT proteins predominantly utilized by IL-12 and IFNγ respectively (Oestreich et al., 2012, Curr Opin Immunol 24: 191-195) and Irf8 and Batf. At 24hrs, IL-12+IFNγ uniquely induced Id2 and repressed Id3 (FIG.12C), two TFs known to reciprocally promote TH1 and TFH differentiation by blocking Bcl6 and Blimp-1 expression respectively (Shaw et al., 2016, Nat Immunol 17: 834-843). Id3 also suppresses PB differentiation (Gloury et al., 2016, J Exp Med 213: 1095-1111). Comparing the 24 hour DEGs to T cell subset gene sets by GSEA revealed significant enrichment of TH1signature genes in IL-12-stimulated cells and Treg signature genes among both IFNγ and IL-12+IFNγ stimulated cells (FIG.14). GSEA also showed that B cell proliferation genes were enriched among both IL-12 and IFNγ alone and in the two in combination (FIG.14). IFNγ at 24 hours also induced Cxcr3, along with transcripts for both known CXCR3 ligands, Cxcl9 and Cxcl10. This receptor and its ligand mediate migration towards inflammation (Hauser et al., 2002, J Immunol 169: 1277-1282; Muehlinghaus et al., 2005, Blood 105: 3965-3971). Collectively, in combination with our in vitro assays, RNA-seq data support a model of a positive feedback loop (FIG.12F), in which IL-12 induces expression of IFNγ, which induces inhibitors that downregulate IFNγ signaling, but also promotes expression of the IL-12R subunits and STAT4. Higher expression of IL-12R in turn would enhance the sensing of IL-12, which as outlined above works to sustain IFNγ effects, resulting in a positive- feedback network. EXAMPLE 10: In vivo B cell derived IL-12 influences both B and T cells To test the in vivo roles of the positive feedback loop driven by B cell-derived IL-12 and IFNγ, it was determined whether IL-12 induces IFNγ production in the absence of STm infection. Indeed, administering IL-12 during NP-CGG immunization promoted IFNγ production from B cells (FIGs.15A- 15B). Some, but not all, IFNγ-producing B cells co-expressed T-bet (FIGs.16A-16B). To determine whether B cell production of IL-12 contributes to PB differentiation in vivo, and whether it is direct or indirect, B and T cells lacking IL12p40 or IL12Rb2 were cotransferred, respectively (FIG.15C), then immunized recipients in the presence of HK Stm. This receptor-cytokine subunit pair excludes contributions from the related cytokines IL-23 and IL-35 in cognate interactions (Tait et al., 2019, Immunity 50: 851-870). IL-12 production from B cells was necessary for a maximal PB response, independent of IL-12R expression on CD4 T cells (FIG.15D, FIGs.16C-16E). In all conditions B cells lacking IL12p40 produced significantly fewer IgM AFC, except for NP-specific IgM AFC when T cells also lacked the IL-12R (FIG.15E). IRF4 expression was reduced on B cells that could not make their own IL-12 (FIG.16E). Therefore, IL-12 produced by B cells promotes PB differentiation in vivo, which is generally independent of T cell sensing of IL-12. Notably, the frequency of IFNγ+WT T cells was enhanced when B cells could produce IL-12 (FIG. 15F, FIGs.16F-16G), demonstrating that B cell-derived IL-12 promotes TH1differentiation in vivo. The frequency of IFNγ+IL-12R KO T cells on the other hand was unaffected by B cell genotype, as may be expected since these T cells cannot sense IL-12. The ability of these T cells to produce IFNγ+may be related to an overall dysregulation of T-bet and Bcl6 observed in T cells that cannot sense IL-12, as these cells aberrantly co-expressed T-bet and Bcl6 in contrast to WT T cells (FIGs.15F-15G). Inappropriate co- expression of T-bet and Bcl6, as only seen in mutant IL-12R-deficient T cells, could lead to an unstable TH1 phenotype. In support of this, IL-12R KO T cells produced higher frequencies of early TFH (FIGs.16H-16I), consistent with the report that IL-12 suppresses murine TFHdifferentiation in vivo (Elsner et al., 2019, Cell Rep 29: 2796-2809). Finally, to determine whether IL-12 and IFNγ have non-redundant effects on B cell differentiation in vivo, IL-12R KO, IFNgRKO, or IL-12R / IFNgR double KO B cells were compared for the ability to make PB, using three sets of 50 / 50 mixed BM chimeras. HK bacteria was used to stimulate a moderate inflammatory milieu and normalized contributions of each genotype to PB and GC at day 12 was analyzed. IL-12R / IFNgR double KO cells were more strongly disadvantaged in PB generation than either IFNgR KO or IL-12R KO alone, demonstrating that IL-12 and IFNγ signals play non-redundant and at least partially independent roles in controlling PB differentiation in vivo (Fig.15I). A small but significant advantage for GC was observed for double KO cells, consistent with the lower inflammatory environment of HK controls (Fig.15I). The importance of the expression of both IL-12R and IFNgR for PB formation was confirmed even in the context of higher IL-12 / IFNγ during STm infection (Fig.15I). This result argues for a critical role of IL-12 / IFNγ synergy in vivo even in relatively higher inflammatory environments. A positive feedback loop between IL-12 and IFNγ is herein identified, which promotes PB differentiation and suppresses GC formation. Notably, as B cells can make and respond to both cytokines, this feedback loop can be autocrine. However, this B cell circuit can also cross-talk with T cells that respond to IFNγ and IL-12 and make IFNγ. IL-12 initiates the loop by inducing IFNγ, whereas IFNγ does not induce its own production. Indeed, IFNγ was one of the very few genes induced at early time points in vitro with IL-12 stimulation. B cells could initiate the feedforward themselves by making IL-12 in response to innate and BCR stimuli, but other innate cells such as DCs and macrophages (Tait et al., 2019, Immunity 50: 851- 870) are also a likely source of IL-12 to prime the reaction in vivo. The positive feedback loop that amplifies IL-12R signaling and thereby IFNγ production in B cells, in turn allows dose-dependent effects of IFNγ to amplify B cell expansion and PB differentiation (FIG. 16K). In vivo, B cell autocrine IL-12 was necessary for maximal PB production. A mechanism by which the B cell-intrinsic positive feedback loop propagates is via IFNγ inducing the expression of both Il12rb1 and Il12rb2, and Stat4, also necessary for IL-12R signaling (Tait et al., 2019, Immunity 50: 851-870). The upregulation of these genes likely makes such B cells more sensitive to IL-12, thus in turn inducing two major positive feedback effects of IL-12R signaling: further dose-dependent IFNγ secretion, and sustained expression of IFNγ-induced genes, as demonstrated in the RNA-seq time course. The effects of IL-12 on T cells are known (Kobayashi et al., 1989, J Exp Med 170: 827-845), while the parallel effects on B cells were not previously elucidated. The feedforward IL-12 / IFNγ loop that can operate in the context of innate (e.g. TLR) or BCR-driven (e.g. the Ag-specific response to STm (Di Niro et al., 2015, Immunity 43: 120-131)) signals, or both. Hence, for B cells this cytokine circuit provides for self- sufficient responses, as occurs in various contexts in vivo. These include responses to T-independent antigens such as bacterial glycoepitopes; TLR-driven, B cell-directed autoimmune responses; early primary responses when antigen-specific T cells may be limiting; and in certain responses in tissues (e.g. to Ehrlichia in the liver (Trivedi et al., 2019, Immunity 51: 1088-1101)). T-independent B cell proliferative foci observed in such situations are clusters of cells with a mixture of proliferative B cell blasts and differentiating plasmablasts. As the circuit orchestrated by the interplay of IFNγ and IL-12 secretion and sensing can regulate proliferation, cell death (which is greater in the presence of IL-12), and differentiation, it was found that the combination of autocrine and paracrine local cytokine concentrations serves to shape and limit the size of the responding B cell clonal cluster, modulating the fraction of cells that is proliferating vs differentiating. Activated B cells are sensitive to very low cytokine concentrations and display qualitatively different responses that are dose-dependent. In contrast to the design in B cells, CD4 T cells do not produce IL-12, and IFNγ is not sufficient for TH1differentiation (Schulz et al., 2009, Immunity 30: 673-683). Thus, unlike B cells, CD4 T cells are not capable of a cell-autonomous clonal burst driven by an IL-12 / IFNγ feedforward circuit; instead, they would need to obtain at least intermittent supplies of IL-12 from another cell to enable the TH1- and proliferation- driving effects of IFNγ to be maintained. This requirement limits overexuberant T cell responses that could result in pathology. Furthermore, IL-12 is needed sequentially for TH1 differentiation, first to induce and later to stabilize T-bet expression (Schulz et al., 2009, Immunity 30: 673-683), raising the possibility that the later exposures to IL-12 in vivo comes from B cells. In support of this, in mixed cell transfers, T cells had reduced TH1and more TFHdifferentiation when only B cells could not produce IL-12. The results presented herein evidence that IL-12 as a dominant upstream regulator of adaptive immunity per se, with its parallel roles in both T and B cells. IL-12 functions as a switch to coordinate adaptive immunity towards immediate effector functions. When IL-12 is absent, responses take on a less inflammatory character and focus more on the creation of long-lived immunity, through the development of GC B cells and TFH, which are the alternatives to the extrafollicular B cell PB and TH1response. Thus IL-12 modulates responses in one direction or another in the context of vaccination, acute serious infection, and autoimmunity. The results presented herein provide parameters that can be measured to determine which subjects will respond to treatment with an IL-12 antagonist. EXAMPLE 11: IL-12 and IFNγ have similar effects on human cells B cells isolated from spleens of seven organ donor individuals were cultured with CpG DNA and combinations of IL-12, IFNγ, or blocking antibodies and examined proliferation and PB differentiation after 8 days. FIG.18A shows an example of flow cytometry analysis of B cell proliferation and differentiation to CD38hiIRF4hiPB, and their frequency among each division number. FIG.18B shows a representative example of PB differentiation (CD38hiIRF4hi) for donor B cells cultured under each indicated cytokine condition. Compared to CpG alone, blocking endogenously produced IL-12 and IFNγ reduced the percentages of PB and proliferation in the cultures (FIGs.18B-18D), although such blocking did not significantly reduce PB differentiation per division (FIG.18E). Adding IL-12 alone (while blocking IFNγ) resulted in significantly increased total numbers of PB compared to blocking both, but effects on proliferation and differentiation individually were smaller. Most importantly, IL-12 or IFNγ alone, in the absence of blocking antibodies and hence permissive of synergy from B cell-derived IFNγ, significantly increased PB frequencies and proliferation (Fig.18C); these cytokines also increased PB generation per division for some donors (Fig.18E). Together these data indicate that IL-12 in human B cells, whether endogenously produced or exogenously provided, promotes proliferation and PB differentiation by inducing IFNγ production from B cells. Example 12: IL-12 enhances responses to IFNγ via increasing production of IFN as well as via synergistic gene induction The production of IL-12 and IFNγ by mouse B cells was quantified after treatment with optimal (200 pg / mL IL-12 and 10 ng / mL IFNγ) or suboptimal concentrations (20 pg / mL IL-12 and 0.25 ng / mL IFNγ) of each cytokine over 24 hours (FIG.19A) and 3 or 4 days (FIG.19B). This was performed without blocking antibodies to allow positive feedback (“-“ indicates no addition in the figure). At 24 hours there was not significantly increased IL-12 or IFNγ in culture supernatants compared to either added alone (FIG. 19A), suggesting a synergistic effect of IL-12 and IFNγ on gene expression (FIGs.12A-12F, 13A-13D). IL- 12 added to the cultures stimulated the production of IFNγ, while IFNγ supported the production of small amounts of IL-12, consistent with a proposed positive feedback loop (FIG.19A). Even at days 3 and 4 of culture, IL-12 added at 200 pg / mL only resulted in approximately 2 ng / mL of IFNγ (FIG.19B), not reaching the 10 ng / mL IFNγ needed to generate equivalent degrees of PB differentiation without IL-12 (Fig.7D). Additionally, serum IL-12 and IFNγ after STm infection were in a range consistent with the concentrations necessary to observe synergy effects in vitro (FIG.19C). Naïve and HK STm controls did not contain detectable amounts of either cytokine in the serum, as expected. Example 13: IL-12 contributes to autoimmune disease and as a therapeutic target To test the role of IL-12 without the confounding effects of simultaneously targeting a related pro- inflammatory cytokine IL-23, IL-12Rb2 knock out MRL / lpr mice were constructed by CRISPR targeting. The MRL / lpr mouse model is an art-accepted mouse model for lupus-like disease, a type of systemic autoimmune disease. The IL-12R2b subunit of the IL-12 receptor is shared between IL-12 and IL-35 receptors, but importantly is not part of the IL-23 receptor. IL-35 is an anti-inflammatory cytokine that protects from lupus disease in MRL / lpr mouse models (Cai et al., 2015, Clin Exp Immunol 181, 253-266). Therefore, any disease reduction observed in IL-12Rb2 KO MRL / lpr mice would be due to the loss of pro- inflammatory IL-12, not IL-35 (nor IL-23). Indeed, compared to co-housed wild-type (WT) littermate controls, IL-12R KO MRL / lpr (KO) mice had reduced lupus-like disease, including reduced skin disease and proteinuria (a measure of kidney disease) (FIG.20A) as well as increased survival (FIG.20B). The data shown are from female mice, as lupus disease is more prevalent and severe in females (mouse and human) . These data support a role for IL-12 in initiation and / or promotion of systemic autoimmune disease. Targeting IL-12 specifically can be a beneficial treatment option, as compared to drugs that target both IL- 12 and IL-23. It is notable that IL-12Rb2 KO MRL / lpr mice were not completely free of disease (FIG.20). This may be explained by combinatorial effects and / or non-redundant roles of IL-12 and IFNγ in promoting pathogenic cell types, such as PB and Th1 cells. Very high concentrations of IFNγ can be sufficient to promote PB differentiation in vitro (FIG.7D), and IL-12 and IFNγ are elevated in SLE patients (Tokano et al., 1999, Clin Exp Immunol 116, 169-173 ). Thus, combined blockade of IL-12 and IFNγ could be most efficacious in blocking this type of inflammation. Supporting this, B cells lacking IL-12R had a less severe loss in PB than cells lacking both IL-12R and IFNgR (FIG.21, top). In contrast, Th1 cells are far more sensitive to the loss of IL-12R (Fig.21, bottom). Therefore, while the loss of IL-12R on B cells can be compensated by an excess of IFNγ, Th1 cells strictly require IL-12R, indicating different cell intrinsic requirements for each cytokine and supporting the potential need for a dual-blockade approach to fully suppress disease. However, long-term blockade of both cytokines may put patients at risk of complications due to infection. A short “induction therapy” course of IL-12+IFNγ dual blockade, followed by maintenance therapy with only IL-12 blockade, can be an effective course of treatment. Without being bund by theory, this combination can balance treating the underlying inflammation that promotes and sustains systemic autoimmune disease with the risk for complications from immune suppression. Systemic autoimmune diseases are heterogenous. For example, while a great majority of SLE patients show an “IFN signature”, only approximately 50% of patients respond to type I IFN blockade (Bruce et al., 2022, Ann Rheum Dis 81, 962-969; Morand et al., 2020, N Engl J Med 382, 211-221). Current methods do not reliably distinguish type I IFN (α and β) versus type II IFN (γ) “IFN signatures.” This may indicate that IFNγ is the driving factor in the 50% of patients that don’t respond to type I IFN blockade, and such patients would benefit most from IL-12 / IFNγ blockade. Biomarkers of IL-12 / IFNγ driven disease can be used to identify patients most likely to benefit from this treatment. Towards this, candidates include the differentially expressed genes in FIGs.12A-12F and 13A-13D. Further validation, at a protein level, is data that CXCR3 and CD326 are upregulated in an IFNγ dependent way on mouse B cells in vivo (FIG.22A) using the previously described mixed bone marrow chimeras (FIG.3A), and that CXCR3 is upregulated on human B cells following IL-12 / IFNγ treatment (FIG.22B), using the human B cell culture system described in FIG.18. These and other differentially expressed genes from FIGs.12A-12F and 13A- 13D can be used to detect IL-12 / IFNγ driven disease in autoimmune patients. EXAMPLE 14: Clinical Study A. Enrollment / Eligibility • A documented medical history to meet SLICC classification criteria for SLE for a minimum of 3 months prior to first dose. • At least one well-documented (subject file, referring physician letter, or laboratory result), unequivocally positive, documented test for autoantibodies in medical history including either of the following: anti-nuclear antibodies (ANA), and / or anti-dsDNA antibodies, and / or anti-Smith antibodies. • At least one unequivocally positive autoantibody test including ANA and / or anti-dsDNA antibodies and / or anti-Smith antibodies detected during screening • At least one British Isles Lupus Assessment Group (BILAG) A and / or 2 BILAG B domain scores observed during screening prior to first administration of study agent. • Demonstrate active disease based on Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K score greater than or equal to (>=) 6 observed during screening and assessed approximately 2 to 6 weeks prior to study initiation. Should also have SLEDAI-2K score >= 4 for clinical features (i.e., SLEDAI excluding laboratory results) at Week 0 prior to the first administration of study agent. B. Stratification Eligible subjects are further evaluated and can be enrolled in the study if they show: increased DN cells (IgDneg / CD27neg) and / or plasmablasts (CD38hi / IRF4hi / CD138hi) in a peripheral blood sample obtained from the subject, defined as 10% or more of total CD19+ cells or >10 DN2 positive (i.e. IgDneg / CD27neg / CD11c+) cells per microliter of blood; ii) an increase of T-bet, CXCR3, CD326, V-domain Ig suppressor of T cell activation (VISTA), Ly6H CD317 and / or IFNγ expressing lymphocytes in a peripheral blood sample obtained from the subject, defined as 10% of more of total CD19+ cells; iii) elevated serum concentration of IL-12 and / or IFNγ, defined as >55pg / ml and 25pg / ml, respectively; and iv) elevated anti-RNA or anti-SM antibodies in a blood sample obtained from the subject as compared to standard controls. C. Treatment Subjects are administered a therapeutic amount of an IL-12 neutralizing antibody intravenously once every four weeks for a total of six doses and then evaluated at 24 weeks. Therapeutic doses will be determined in preliminary studies but can include 30, 60 or 90mg per infusion or 2, 4, or 6 mg / kg. Dosing is stopped for any infection that is deemed potentially of bacterial origin. D. Evaluation The primary endpoint of the study is a positive SRI-4 response, defined as greater than or equal to 4- point reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) total score, no new British Isles Lupus Assessment Group (BILAG) A and no more than 1 new BILAG B domain score and no worsening (less than 10 percent increase) from baseline in Physician's Global Assessment of Disease Activity (PGA). Composite response is defined as SRI-4 response in participants who do not meet treatment failure criteria. SLEDAI-2K assessment consists of 24 items with total score of 0 to 105, with higher scores representing increased disease activity. BILAG Index: assessing clinical signs, symptoms, or laboratory parameters related to SLE, divided into nine organ systems. For each organ system: A=severe disease, B=moderate disease, C=mild stable disease, D=inactive, but previously active, E=inactive and never affected. The PGA assesses disease activity on a visual analogue scale = from very well (0)-very poor (10). Serum cytokine levels of IL-12, IL-2, IFNγ, IFN-I, IL-23, IL-35, IL-10, IL-21, IL-18 is measured at baseline and at 12 and 24 weeks. Reduction of IL-12 levels are considered a secondary endpoint. It will be apparent that the precise details of the methods or compositions described may be varied or modified without departing from the spirit of the described aspects of the disclosure. We claim all such modifications and variations that fall within the scope and spirit of the claims below.

Claims

We claim:

1. A method of treating a subject with an autoimmune disease, comprising: a. selecting a subject with the autoimmune disease that has i) an increase in ABC, DN1 cells, DN2 cells, DN3 cells, and / or plasmablasts in a biological sample obtained from the subject as compared a control, ii) an increased level of T-bet, CXCR3, CD326, V-domain Ig suppressor of T cell activation (VISTA), Lymphocyte antigen 6 family member H (Ly6H), CD317 and / or interferon (IFN)γ expressing lymphocytes in a biological sample obtained from the subject as compared to a control; iii) elevated serum concentration of interleukin (IL)-12 and / or IFNγ as compared to a control, and / or iv) elevated anti-RNA or anti-Smith (Sm) antibodies in a biological sample obtained from the subject as compared to a control, and b. administering to the subject an effective amount of IL-12 antagonist, thereby treating the autoimmune disease in the subject.

2. The method of claim 1, wherein the autoimmune disease is systemic lupus erythematosus (SLE), Sjogren’s syndrome, alopecia areata, ankylosing spondylitis, anti-phospholipid antibody syndrome, autoimmune hepatitis, Celiac disease, Crohn’s disease, Goodpasture’s Syndrome, Grave’s disease, Hashimoto’s thyroiditis, immune thrombocytopenia, IgA Nephropathy, inflammatory bowel disease (IBD), multiple sclerosis, myasthenia gravis, pemphigoid, pemphigus, polyglandular autoimmune syndrome type 2, psoriasis, psoriatic arthritis, rheumatoid arthritis, scleroderma, Takayasu’s arteriosus, type 1 diabetes, ulcerative colitis, or undifferentiated connective tissue disease (UCTD).

3. The method of claim 2, wherein the autoimmune disease is systemic lupus erythematosus (SLE).

4. The method of claim 3, wherein the subject has nephritis and / or skin disease.

5. The method of claim 2, wherein the autoimmune disease is Sjogren’s syndrome.

6. The method of any one of claims 1-5, wherein the method further comprises administering to the subject an effective amount of Belimumab, Anifrolumab or Rituximab.

7. The method of any one of claims 1-6, wherein the method further comprises administering to the subject an effective amount of interferon (IFN)-γ antagonist.

8. The method of claim 7, wherein the IFNγ antagonist is an antibody that specifically binds IFNγ.

9. The method of claim 8, wherein the antibody that specifically binds IFNγ is Emapalumab.

10. The method of any one of claims 1-9, wherein the IL-12 antagonist is an antibody that specifically binds IL-12.

11. The method of claim 10, wherein the antibody that specifically binds IL-12 is Ustekinumab.

12. The method of claim 10, wherein the antibody specifically binds IL-12 p70.

13. The method of any one of claims 1-12, wherein the subject is human.

14. The method of any one of claims 1-13, wherein the method comprises measuring the ABC cells in a biological sample obtained from the subject.

15. The method of any one of claims 1-14, wherein the method comprises measuring the DN1 cells, DN2 cells, or DN3 cells in a biological sample obtained from the subject.

16. The method of any one of claims 1-13, wherein the method comprises measuring the plasmablast cells in a biological sample obtained from the subject.

17. The method of any one of claims 1-16, wherein the method comprises measuring the T-bet expressing lymphocytes in a biological sample obtained from the subject.

18. The method of any one of claims 1-17, wherein the method comprises measuring the CXCR3 expressing lymphocytes in a biological sample obtained from the subject.

19. The method of any one of claims 1-18, wherein the method comprises measuring the CD326 expressing lymphocytes in a biological sample obtained from the subject.

20. The method of any one of claims 1-19, wherein the method comprises measuring the VISTA expressing lymphocytes in a biological sample obtained from the subject.

21. The method of any one of claims 1-20, wherein the method comprises measuring the Ly6H expressing lymphocytes in a biological sample obtained from the subject.

22. The method of any one of claims 1-21, wherein the method comprises measuring the CD317expressing lymphocytes in a biological sample obtained from the subject.

23. The method of any one of claims 1-22, wherein the method comprises measuring the IFNγ expressing lymphocytes in a biological sample obtained from the subject.

24. The method of any one of claims 1-23, wherein the method comprises measuring the serum IL-12 and / or IFNγ concentration in a biological sample obtained from the subject.

25. The method of any one of claim 1-24, wherein the control is the amount of: i) ABC, DN1 cells, DN2 cells, DN3 cells, and / or plasmablasts, ii) the T-bet, CXCR3, CD326, VISTA, Ly6H, CD317 and / or IFNγ expressing lymphocytes; iii) serum concentration of IL-12 and / or IFNγ, and / or iv) elevated anti- RNA or anti-SM antibodies, respectively, in a biological sample obtained from a subject that does not have the autoimmune disease.

26. The method of any one of claims 1-25, wherein the biological sample is a blood sample.

27. A composition comprising a therapeutically effective of an IL-12 antagonist for use in the method of any one of claims 1-26.

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