Figure 7. Dampening of inflammatory signals rescues GC differentiation in Arid1a-deficient B cells.

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 (redboxes) and CD45.1 GC B cells (dark grey boxes) within total GC B cells from SRBC immunized Arid1a fl/fl and Cg1 Arid1aKOchimeras 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, see dashed arrows. 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. Arid1a fl/fl and Cg1 Arid1aKO chimeras treated with DMSO are open bars and Dexa treated groups are represented with light red filled bars. D and E. Quantification of YFP frequency (C) and absolute numbers (D) gated on CD45.2 GC B cells from Arid1a fl/fl or Cg1 Arid1aKO chimeras. F. 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 C and two-tailed Student’s t-test for D and E. Error bars represent mean ± s.e.; *p value ≤ 0.05; **p value ≤ 0.01; ***p value ≤ 0.0005; ****p value < 0.0001.