Arid2 regulates peripheral B cell maturation and germinal-center responses in vivo.

Abstract

SWI/SNF chromatin remodeling complexes regulate gene expression during development and differentiation. These complexes exist in distinct forms, including the polybromo-associated BAF (PBAF) complex, defined by the ARID2 subunit. ARID2 is frequently mutated in B cell leukemias, but its role in normal B cell development remains unknown. Using Mb1-Cre and CD19-Cre conditional mouse models, we show that Arid2 is required for normal peripheral B-cell maturation. Early deletion with Mb1-Cre caused marked reductions in splenic T1 and T2 transitional B cells, follicular B cells, and recirculating B cells, whereas later deletion with CD19-Cre produced a milder follicular B cell phenotype but a similar reduction in transitional B cells. Bone-marrow progenitor and immature B cell populations were largely preserved, suggesting that the developmental defect emerges during peripheral transitional maturation and follicular B cell differentiation. Transcriptomic profiling of isolated pro-B, pre-B, and follicular B cells revealed that Arid2 loss caused progressive, stage-specific transcriptional dysregulation, including altered AP-1-associated programs and reduced B cell receptor-associated signaling in pre-B and follicular B cells. Functionally, mice with Mb1-Cre-mediated Arid2 deletion mice formed smaller germinal center B cell populations after immunization but maintained total and antigen-specific IgG responses and exhibited increased IgM responses. Together, these findings establish an important role for Arid2 in peripheral B cell maturation and germinal center responses.