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Arid1a-dependent canonical BAF complex suppresses inflammatory programs to drive efficient germinal center B cell responses

Nature Immunology volume 25, pages 1704–1717 (2024)Cite this article

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Abstract

The mammalian Brg1/Brm-associated factor (BAF) complexes are major regulators of nucleosomal remodeling that are commonly mutated in several cancers, including germinal center (GC)-derived B cell lymphomas. However, the specific roles of different BAF complexes in GC B cell biology are not well understood. Here we show that the AT-rich interaction domain 1a (Arid1a) containing canonical BAF (cBAF) complex is required for maintenance of GCs and high-affinity antibody responses. While Arid1a-deficient B cells undergo initial activation, they fail to sustain the GC program. Arid1a establishes permissive chromatin landscapes for B cell activation and is concomitantly required to suppress inflammatory gene programs. The inflammatory signatures instigated by Arid1a deficiency promoted the recruitment of neutrophils and inflammatory monocytes. Dampening of inflammatory cues through interleukin-1β blockade or glucocorticoid receptor agonist partially rescued Arid1a-deficient GCs, highlighting a critical role for inflammation in impeding GCs. Our work reveals essential functions of Arid1a-dependent cBAF in promoting efficient GC responses.

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Fig. 1: Arid1a deficiency in B cells perturbs germinal center B cell responses.
Fig. 2: Arid1a is required for induction and maintenance of GCs.
Fig. 3: Arid1a-deficient B cells undergo activation in vitro.
Fig. 4: Arid1a deficiency is associated with induction of inflammatory signatures.
Fig. 5: Arid1a-deficient B cells fail to sustain GCs.
Fig. 6: Arid1a deficiency promotes infiltration of inflammatory myeloid cells.
Fig. 7: IL-1β blockade rescues GC differentiation in Arid1a-deficient B cells.

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Data availability

All genome-wide sequencing datasets have been deposited to Gene Expression Omnibus (GEO) repository, accession number GSE246913. Any other data and reagents will be made available upon request. Source data are provided with this paper.

Code availability

The code used to process the next-generation sequencing datasets is deposited to GitHub (https://github.com/dsamanie7/Arid1A_KO_Bcells).

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Acknowledgements

We thank L. Arispe, S. Eisenbarth and W. Cui for critical reading of our paper and D. Kitamura at the Tokyo University of Science for sharing the 40LB cells. We thank X. Wang and M. Schipma and other members of the Northwestern University Sequencing Core for providing next-generation sequencing services, the Northwestern University RHLCCC Flow Cytometry Facility team (S. Swaminathan, C. Ostiguin, E. Dias and others) for their help with cell sorting and the Northwestern University Center for Advanced Microscopy (CAM) team members (C. Arvanitis and W. Liu) for helping with the imaging experiments. The RHLCCC Flow Cytometry Facility acknowledges support from the Cancer Center grant NCI CA060553, NIH 1S10OD011996-01 and 1S10OD026814-01. The CAM core acknowledges support from NCI CCSG P30 CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center. Histology services were provided by the Northwestern University Mouse Histology and Phenotyping Laboratory, which is supported by NCI P30 CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center. The schematics (Figs. 1c, 3a, 5c, 6i and 7a and Extended Data Figs. 2i, 8h and 9a) were created using BioRender.com. R.C.M. is supported by The Ruth L. Kirschstein NRSA Institutional Research Training Grant (T32) (grant no. 5T32AI083216-15; Northwestern University Allergy and Immunology Research Program Training Grant, NUAIR). This work was supported by the R00 award from the National Cancer Institute (grant no. R00CA248835) and institutional startup funds from Northwestern University and the Lurie Cancer Center (to V.S.).

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Author notes

  1. These authors contributed equally: Ajay Abraham, Daniela Samaniego-Castruita.

Authors and Affiliations

  1. Department of Cell and Developmental Biology, Northwestern University, Chicago, IL, USA

    Ajay Abraham, Daniela Samaniego-Castruita, Isabella Han, Prathyaya Ramesh, Mi Thao Tran, Jillian Paladino, Heather Kligfeld, Roxroy C. Morgan, Rebecca L. Schmitz, Rebecca M. Southern, Ashima Shukla & Vipul Shukla

  2. Center for Human Immunobiology, Northwestern University, Chicago, IL, USA

    Ajay Abraham & Vipul Shukla

  3. Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA

    Vipul Shukla

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Contributions

A.A. acquired, analyzed and interpreted the data. D.S.-C. and V.S. performed the bioinformatics analysis. J.P. performed the antibody measurement assays. I.H. assisted with next-generation sequencing library preps. P.R. performed the imaging analysis. M.T.T., I.H., R.C.M., H.K., R.L.S. and R.M.S. performed flow cytometry experiments. A.S. and V.S. supervised the studies, conceptualized the experiments and helped with the interpretation of data. A.A., D.S.-C. and V.S. wrote, and all members of the Shukla laboratory reviewed, the paper. All authors were involved in reviewing and editing the paper.

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Correspondence to Vipul Shukla.

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Nature Immunology thanks Marcus Clark and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Peer reviewer reports are available. Primary Handling Editor: L. A. Dempsey, in collaboration with the Nature Immunology team.

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Extended data

Extended Data Fig. 1 CD19 Arid1a KO mice display normal B cell development.

a. Representative flow cytometry analysis of bone marrow (BM) B cell subsets from Arid1a fl/fl (YFP-) and CD19 Arid1a KO (YFP+) mice. Numbers represent frequencies of pre and pro B cells (pre/proB), Immature B cells, mature B cells and recirculating B cells. b. Quantification of BM B cell subsets from Arid1a fl/fl (YFP-; n = 5) and CD19 Arid1a KO (YFP+; n = 5). c. Immunoblot showing Arid1a expression from Arid1a fl/fl and CD19 Arid1a KO naïve B cells. Beta-actin (β-actin) is used as loading control. d-f Quantification of spleen cellularity, B cell frequency and numbers from Arid1a fl/fl (YFP-; n = 5) and CD19 Arid1a KO (YFP+; n = 5). g. Representative flow cytometry plots quantifying percent apoptotic cells as cleaved Caspase-3 staining from Arid1a fl/fl (YFP-; n = 3) and CD19 Arid1a KO (YFP+; n = 3) naïve B cells. h. Quantification of apoptotic B cells (cleaved Caspase-3 positive) from Arid1a fl/fl and CD19 Arid1a KO mice. i. Representative flow cytometry plots quantifying percent proliferating cells with Ki67 staining from Arid1a fl/fl (YFP-; n = 3) and CD19 Arid1a KO (YFP+; n = 3) naïve B cells. j. Quantification of proliferation (Ki67 positive) from Arid1a fl/fl and CD19 Arid1a KO mice. Statistical significance is calculated using multiple unpaired t-tests for B and two-tailed Student’s t-test for d, e, f, h and j. Error bars represent mean ± s.e.; *p value ≤ 0.05; **p value ≤ 0.01; ***p value ≤ 0.0005; ****p value < 0.0001.

Source data

Extended Data Fig. 2 Characterization of peripheral B cell compartment in CD19 Arid1a KO mice.

a. Representative flow cytometry analysis of mature (AA4.1- B220+) and immature B cells (AA4.1+ B220+) subsets from splenic B cells in Arid1a fl/fl (YFP-) and CD19 Arid1a KO (YFP+) mice. b. Quantification of splenic mature and immature B cell subsets from Arid1a fl/fl (YFP-; n = 5) and CD19 Arid1a KO (YFP+; n = 5) mice. c and d. Quantification of splenic Follicular (FO) B cells (IgD hi, IgM low) and Marginal zone (MZ) B cells (IgD low, IgM hi) from Arid1a fl/fl (YFP-; n = 5) and CD19 Arid1a KO (YFP+; n = 5) mice. e. Representative flow cytometry analysis showing YFP expression in B cells (left panel) and GC B cells (right panel) from Peyer’s patches of CD19 Arid1aKO mice. f. Representative flow cytometry analysis showing YFP reporter expression in GC B cells (middle panel) and non-GC B cells (right panel) from SRBC immunized Cg1 cre Rosa26 loxp-stop-loxp YFP reporter mice. g. Representative flow cytometry analysis of splenic GC B cells gated on B cells from NP-Ova immunized Arid1a fl/fl, Cg1 Arid1a fl/+(Het) and Cg1 Arid1a KO mice at 14 days post-immunization. h. Quantification of GC B cell frequency in spleen of Control (Ctrl) (both Arid1a fl/fl and Cg1 cre; n = 12), Cg1 Arid1a fl/+(Het) (n = 4) and Cg1 Arid1a KO (n = 6) mice. i. Schematic of a flow cytometry-based assay to quantify SRBC-specific IgM and IgG1 antibodies in the sera. j and k. Quantification of serum SRBC-specific IgM and IgG1 antibodies upon SRBC immunization in Ctrl (Arid1fl/fl and Cg1 Cre; n = 4) and Cg1 Arid1aKO mice (n = 4). Statistical significance is calculated using multiple unpaired t-tests for b and two-tailed Student’s t-test for c, d, j and k, and one-way ANOVA for h. Error bars represent mean ± s.e.; *p value ≤ 0.05; **p value ≤ 0.01; ***p value ≤ 0.0005; ****p value < 0.0001.

Extended Data Fig. 3 Arid1a deficiency does not have a major impact of B cell activation in vitro.

a. Representative flow cytometry analysis showing YFP expression in Cg1 Arid1a KO B cells at pre- and post-stimulation (day 4) on 40LB co-cultures with IL4 (in vitro). b. Representative flow cytometry analysis showing GL7 expression in Cg1cre (controls) and Cg1 Arid1a KO B cells at day 4 of in vitro 40LB co-culture. c. Representative flow cytometry analysis of IgD and IgM expression from Arid1a fl/fl (YFP-) and CD19 Arid1a KO (YFP+) splenic B cells. The median fluorescence intensity (MFI) for IgD in quadrant1 (Q1) is shown in the plots. d. Representative flow cytometry analysis quantifying percent apoptotic cells (cleaved Caspase3) from Cg1 cre (n = 4) and Cg1 Arid1a KO (n = 3) B cells at day 4 in vitro 40LB co-cultures. e. Quantification of apoptotic B cells (cleaved Caspase 3 positive) from Cg1 cre (n = 4) and Cg1 Arid1a KO (n = 3) on 40LB co-cultures. f. Representative flow cytometry analysis of proliferating cells (Ki67 positive) from Cg1 cre and Cg1 Arid1a KO B cells at day 4 of in vitro 40LB co-cultures. g. Quantification of proliferating B cells (Ki67 positive) from Cg1 cre (n = 4) and Cg1 Arid1a KO (n = 3) on 40LB co-cultures. h. Representative flow cytometry analysis quantifying percent plasma cells (CD138+) from Cg1 cre and Cg1 Arid1a KO B cells at day 4 of in vitro 40LB co-cultures. i. Quantification of percent of CD138+ plasma cells from Cg1 cre (n = 4) and Cg1 Arid1a KO (n = 3) B cells at day 4 of in vitro 40LB co-cultures. j. Representative flow cytometry analysis of IgG1 and IgM positive B cells from Arid1a fl/fl and CD19 Arid1a KO mice after 4 days of 40 LB co-cultures. k-l Quantification of IgM and IgG1 frequencies from day 4 of 40LB co-culture (n = 3). m-n. Median fluorescence intensity (MFI) of IgM and IgG1 from day 4 of 40LB co-culture (n = 3). o. Cell counts of Arid1a fl/fl and CD19 Arid1aKO B cells stimulated on 40LB co-cultures for 4 days (n = 3). p-q Quantification of apoptotic (cleaved Caspase 3 positive) and proliferating B cells (Ki67 positive) respectively from Arid1a fl/fl and Cd19 Arid1a KO on 40LB co-cultures (n = 3). r. Representative flow cytometry analysis quantifying percent plasma cells (CD138+) from Arid1a fl/fl and Cd19 Arid1a KO B cells at day 4 of in vitro 40LB co-cultures. s. Quantification of percent of CD138+ plasma cells from Arid1a fl/fl and Cd19 Arid1a KO B cells at day 4 of in vitro 40LB co-cultures (n = 3). Statistical significance is calculated using two-tailed Student’s t-test for e, g, i, k-q, and s. Error bars represent mean ± s.e.; *p value ≤ 0.05; **p value ≤ 0.01; ***p value ≤ 0.0005; ****p value < 0.0001.

Extended Data Fig. 4 Transcriptional and chromatin accessibility profiling of Arid1a-deficient activated B cells.

a-c. GSEA plots for the transcriptional profile of Cg1 Arid1a KO and control B cells, using gene sets from. Pyroptosis (a), Innate immune response (b) and IL-6 production (c) pathways. Y-axis denotes enrichment score. NES, Normalized enrichment score, FDR, False discovery rate. d. Genome browser view of RNA-seq and ATAC-seq data at Igh loci. Asterisks denote changes in accessibility (red and black asterisks denote increased and decreased accessibility signals in Cg1 Arid1a KO cells, respectively). e. Heatmap showing ATAC-Seq signals from individual replicates in differentially accessible regions identified in Cg1 Arid1a KO and control B cells. RPM values in DARs are plotted in +/− 2 kb windows from the center of the peak. f. Aggregate ATAC-seq footprint for RUNX1 and EBF1 (left); CTCF and EGR1 (right) generated over binding sites on Control DARs (left) or KO DARs (right), respectively. g. Scatter plot of log2 fold change DARs (y-axis) and gene expression changes (x-axis) between Cg1 Arid1aKO and control B cells. DEGs associated with a DAR are denoted in color (black: downregulated; red: upregulated in Cg1 Arid1a KO). h-j. Genome browser view of RNA-seq and ATAC-seq data at Socs3 (h); and Prdm1 (i) and Cd72 (j) loci. Asterisks denote regions of interest. Please see bioinformatics analysis in methods for additional information.

Extended Data Fig. 5 Arid1a deficiency does not affect early GC B cell responses.

a. Representative flow cytometry analysis of early GC B cells (PNA+ CD38+) gated from splenic B cells of SRBC immunized Arid1a fl/fl and CD19 Arid1aKO mice at day 4 post-immunization. b. Quantification of PNA+ CD38+ early GC B cell frequency in spleen of Arid1a fl/fl (YFP-) and CD19 Arid1a KO (YFP+) mice at day 4 post-immunization (n = 3). c. Representative flow cytometry plots for EfnB1+CD38+ early GC B cells and EfnB1+ CD38low mature GC B cells gated on splenic B cells from SRBC immunized Arid1a fl/fl (YFP-) and CD19 Arid1aKO (YFP+) mice at day 10 post-immunization. d. Quantification of Irf4 expressing B cells from Arid1a fl/fl and CD19 Arid1a KO mice at day 4 post-SRBC immunization (n = 3). e. Representative flow cytometry analysis of T follicular helper (Tfh) cells gated from CD4+ T cells of SRBC immunized Arid1a fl/fl and CD19 Arid1aKO mice at day 4 post-immunization. f. Quantification of Tfh cell frequency in spleen of Arid1a fl/fl (n = 5) and CD19 Arid1a KO (n = 5) mice at day 4 post-SRBC immunization. g. Representative flow cytometry analysis of Tfh cells gated on CD4+ T cells from SRBC immunized Arid1a fl/fl and CD19 Arid1aKO mice at day 10 post-immunization. h-i. Representative flow cytometry analysis and quantification for Tfh cells gated on CD4+ T cells from NP-Ova immunized Arid1a fl/fl (n = 6) and CD19 Arid1aKO (n = 5) mice at day 14 post-immunization. j-k. Representative flow cytometry plots and quantification for Tfh cells gated on CD4+ T cells from NP-Ova immunized Arid1a fl/fl (n = 7) and Cg1 Arid1aKO (n = 6) mice at day 14 post-immunization. Statistical significance is calculated using two-tailed Student’s t-test for b, d, f, i and k. Error bars represent mean ± s.e.; *p value ≤ 0.05; **p value ≤ 0.01; ***p value ≤ 0.0005; ****p value < 0.0001.

Source data

Extended Data Fig. 6 Transcriptional and chromatin accessibility profiling of Arid1a-deficient early GC B cells.

a-b. Representative flow cytometry analysis and quantification of IgD low CD38+ memory B cell frequencies in Arid1a fl/fl (n = 6) and CD19 Arid1aKO (n = 5) mice at day 14 post-immunization with NP-Ova. c-d. Representative flow cytometry analysis and quantification of NP+ memory B cells identified gated on IgD lo CD38+ memory B cells in Arid1a fl/fl (n = 6) and CD19 Arid1aKO (n = 5) mice at day 14 post-immunization with NP-Ova. e-f. Genome browser view of RNA-seq and ATAC-seq data at Bcl6 (F) and Irf4 (G) loci for CD19 Arid1aKO and control B cells. g-i. Genome browser view of RNA-seq and ATAC-seq data showing gene expression and accessibility enrichment distribution at Ccl3, Ccl4 (g), Il1b (h), Havcr1 (i) and Igh loci (j). Asterisks denote changes in accessibility (red and black asterisks denote increased and decreased accessibility signals in CD19 Arid1a KO cells, respectively). k. Representative flow cytometry analysis of Il1b (pro-form), Ifng and Il6 in Control (Ctrl) (YFP-) and CD19 Arid1aKO (YFP+) non-activated B cells (EfnB1-CD38+) in spleen at day 4 following SRBC immunization. l. Gene set enrichment analysis (GSEA) plots for the transcriptional profile of Cg1 Arid1a KO and control B cells, using gene sets from. Acute inflammatory response (top), Lymphocyte Chemotaxis (middle) and Monocyte Chemotaxis (bottom) pathways in transcription profile of CD19 Arid1aKO and control early GC B cells. Y-axis denotes enrichment score. NES, Normalized enrichment score, FDR, False discovery rate. m. Heatmap showing enrichment of ATAC-seq signal (merge of 2 replicates) in CD19 Arid1aKO and control early GC B cells. RPM values in DARs are plotted in +/− 2 kb windows from the center of the peak. Statistical significance for b and d is calculated using two-tailed Student’s t-test. Error bars represent mean ± s.e.; *p value ≤ 0.05; **p value ≤ 0.01; ***p value ≤ 0.0005; ****p value < 0.0001. Please see bioinformatics analysis in methods for additional information.

Source data

Extended Data Fig. 7 Arid1a deficiency in B cells alters myeloid compartment upon immunization.

a. Representative flow cytometry analysis of splenic CD11b+ myeloid cells in Arid1a fl/fl and Cg1 Arid1aKO mice at day 14 post-immunization with NP-Ova. b. Quantification of CD11b+ myeloid cells frequency in spleen of Arid1a fl/fl (n = 9) and Cg1 Arid1a KO (n = 6) mice at day 14 post-immunization with NP-Ova. c. Representative flow cytometry plots showing neutrophils (Ly6G+Ly6C low) and inflammatory monocytes (Ly6G-Ly6C hi) in Arid1a fl/fl (n = 8) and CD19 Arid1aKO (n = 8) mice at day 10 post-immunization with SRBCs. d. Quantification (absolute numbers) of splenic neutrophils (Ly6G+Ly6C low) and inflammatory monocytes (Ly6G-Ly6C hi) from Arid1a fl/fl and CD19 Arid1aKO mice at day 4 post-immunization with SRBC. e. Representative immunohistochemistry images for PNA, CD11b, Gr1 and CD3e staining on formalin fixed spleen serial sections (displaying the same follicle) from Arid1a fl/fl and CD19 Arid1a KO mice at day 14 post-immunization with NP-Ova. f. Representative flow cytometry plots of CD11b+ bone marrow myeloid cells from Arid1a fl/fl and Cg1 Arid1a KO 40LB co-cultures. g-h. Quantification of CD11b+ myeloid cell frequencies (g) and counts (h) from day 4 of 40LB co-cultures with B cells (n = 4). Statistical significance is calculated using two-tailed Student’s t-test for b, g and h and multiple unpaired t-tests for d. Error bars represent mean ± s.e.; *p value ≤ 0.05; **p value ≤ 0.01; ***p value ≤ 0.0005; ****p value < 0.0001.

Source data

Extended Data Fig. 8 IL-1β blockade in Arid1a-deficient mice reduces myeloid cell infiltration.

a. Quantification of centrocyte (CD83hi CXCR4lo) to centroblast (CD83lo CXCR4hi) ratios (from splenic GC B cells) at day 11 post-immunization from IgG or IL1b blockade. Arid1a fl/fl and CD19 Arid1a KO treated with IgG Ab (n = 5 each) are open bars (black and red respectively) and IL1b blockade groups (n = 5 for Arid1a fl/fl and n = 9 for CD19 Arid1a KO) are represented with purple filled bars and purple open bars respectively. b-c. Quantification of frequencies and numbers of CD11b expressing myeloid cells from IgG or IL1b blockade treated Arid1a fl/fl and CD19 Arid1a KO. d-e. Quantification of frequencies and numbers of Ly6G- Ly6Chi monocytes from IgG or IL1β blockade treated Arid1a fl/fl and CD19 Arid1a KO. f-g. Quantification of frequencies and numbers of Ly6G+ Ly6Clo neutrophils from IgG or IL1b blockade treated Arid1a fl/fl and CD19 Arid1a KO. h. Proposed model by which Arid1a regulates GC responses. On left, Arid1a mediates the establishment of chromatin landscapes required for GC transcriptional program. On right, Arid1a deficiency instigates an inflammatory transcriptional program which recruits inflammatory cell types leading to premature GC collapse. Statistical significance is calculated using 2-way ANOVA with multiple comparisons for all these plots. Error bars represent mean ± s.e.; *p value ≤ 0.05; **p value ≤ 0.01; ***p value ≤ 0.0005; ****p value < 0.0001.

Extended Data Fig. 9 Dexamethasone restores GC B cell differentiation in Arid1a-deficient mice.

a. Schematic for bone marrow transfer (BMT) experiment for evaluating the effects of Dexa on GC B cells from either CD45.2 expressing Arid1a fl/fl or Cg1 Arid1aKO bone marrow (BM) chimeras in CD45.1.2 expressing recipients. b. Representative flow cytometry analysis depicting the distribution of splenic CD45.2 GC B cells (red boxes) and CD45.1 GC B cells (dark grey boxes) within total GC B cells from SRBC immunized Arid1a fl/fl and Cg1 Arid1aKO chimeras at day 11 post-immunization with DMSO or Dexa treatments. The distribution of YFP+ GC B cells from Cg1 Arid1a KO (CD45.2) chimeras treated with DMSO (top) or Dexa (bottom) are shown on the right. c. Quantification of splenic CD45.2 GC B cell frequency normalized to CD45.1 GC B cells within the same mice from Arid1a fl/fl (YFP-) and Cg1 Arid1aKO (YFP+) chimeras at day 11 post-immunization and respective (DMSO and Dexa) treatments. The frequency of each subset was calculated from the live cell gate to account for differences in engraftment. d. Quantification of YFP frequency and absolute numbers gated on CD45.2 GC B cells from Cg1 Arid1aKO chimeras treated with DMSO (n = 4) and Dexa (n = 3). e. Representative flow cytometry analysis depicting the distribution of CD45.2 B cells and CD45.1 B cells from SRBC immunized Arid1a fl/fl and Cg1 Arid1aKO chimeras at day 11 post-immunization. f. Representative flow cytometry analysis of GC B cells from SRBC immunized wild type (WT) mice treated with DMSO or Dexa. Numbers represent frequency of GC B cells at day 11 post-SRBC immunizations and treatment with DMSO or Dexa at days 3, 7 and 9. g. Quantification of GC B cell frequency in spleen of DMSO (n = 5) and Dexa (n = 4) treated SRBC immunized WT mice. h. Quantification of splenic CD45.1.2 GC B cell frequency normalized to CD45.1 GC B cells from Arid1a fl/fl and Cg1 Arid1aKO chimeras at day 11 post-immunization treated with DMSO or Dexa. The frequency was calculated from the live cell gate to account for differences in engraftment. Statistical significance is calculated using two-tailed Student’s t-test for d and g and 2-way ANOVA with multiple comparisons for c and h. Error bars represent mean ± s.e.; *p value ≤ 0.05; **p value ≤ 0.01; ***p value ≤ 0.0005; ****p value < 0.0001.

Extended Data Fig. 10 Effects of dexamethasone on TFH and myeloid cells.

a and b. Quantification of frequencies and numbers of Tfh cells gated on CD45.1 CD4+ cells in Arid1a fl/fl and Cg1 Arid1aKO chimeras at day 11 post-SRBC immunization. Arid1a fl/fl and Cg1 Arid1aKO chimeras treated with DMSO are open bars and Dexa treated groups are represented with light red filled bars. c and d. Quantification of frequencies and numbers of CD11b expressing myeloid cells gated on CD45.1 cells in Arid1a fl/fl and Cg1 Arid1aKO chimeras at day 11 post-SRBC immunization. Arid1a fl/fl and Cg1 Arid1aKO chimeras treated with DMSO are open bars and Dexa treated groups are represented with light red filled bars. e and f. Quantification of frequencies and numbers of Ly6G- Ly6Chi monocytes gated on CD45.1+ CD11b expressing myeloid cells in Arid1a fl/fl and Cg1 Arid1aKO chimeras at day 11 post-SRBC immunization. g and h. Quantification of frequencies and numbers of Ly6G+ Ly6Clo neutrophils gated on CD45.1+ CD11b expressing myeloid cells in Arid1a fl/fl and Cg1 Arid1aKO chimeras at day 11 post-SRBC immunization. i. Quantification of splenocyte numbers in Arid1a fl/fl and Cg1 Arid1aKO chimeras at day 11 post-SRBC immunization with DMSO or Dexa treatment. Statistical significance is calculated using 2-way ANOVA with multiple comparisons. Error bars represent mean ± s.e.; *p value ≤ 0.05; **p value ≤ 0.01; ***p value ≤ 0.0005; ****p value < 0.0001.

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Source Data Extended Data Fig. 1

Unmodified gel images.

Source Data Figs. 1–3 and 5–7

Raw values for all flow cytometry plots in main figures.

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Abraham, A., Samaniego-Castruita, D., Han, I. et al. Arid1a-dependent canonical BAF complex suppresses inflammatory programs to drive efficient germinal center B cell responses. Nat Immunol 25, 1704–1717 (2024). https://doi.org/10.1038/s41590-024-01920-y

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