Arid2 promotes Follicular B-cell differentiation and antibody responses in vivo

SWI/SNF chromatin remodeling complexes, also known as BAF complexes, regulate gene expression during development and differentiation. These complexes exist in distinct variants, including the polybromo-associated BAF (PBAF) complex, defined by the ARID2 core subunit. ARID2 is frequently mutated in B cell leukemias, but its role in normal B cell development remains unknown. Using conditional knockout mice, we show that Arid2 deletion impairs B cell differentiation in vivo. Mb1-Cre–mediated deletion, active in early progenitors, caused a marked reduction of splenic and circulating Follicular B cells, whereas CD19-Cre deletion produced a milder phenotype. These defects were not due to altered proliferation or survival but reflected impaired differentiation potential. Transcriptomic profiling of isolated pro-B, pre-B, and Follicular B cells revealed that Arid2 loss disrupts stage-specific gene expression programs, with cumulative downregulation of B cell receptor signaling and altered lineage-specifying pathways. Functionally, Arid2-deficient mice exhibited impaired germinal center expansion after immunization and reduced IgG antibody production. Together, these findings identify Arid2 as a critical regulator of B cell differentiation and maturation by coordinating transcriptional programs during early lymphopoiesis.