B cell differentiation into germinal center and antibody-secreting cells depends on SMARCA5-mediated chromatin remodeling[CUT & RUN]
The establishment of long-lasting immunity against pathogens is facilitated by the germinal center (GC) reaction, during which B cells increase their antibody affinity, and differentiate into antibody-secreting cells (ASC) and memory cells. These events involve modifications in chromatin packaging that orchestrate the profound restructuring of gene expression networks that determine cell fate. While several chromatin remodelers were implicated in lymphocyte functions, less is known about SMARCA5. Here, by using ribosomal pull-down for analyzing translated genes in GC B cells, coupled with functional experiments in mice, we identified SMARACA5 as a key chromatin remodeler in B cells. While the naive B cell compartment and early B cell activation remained unaffected following conditional depletion of Smarca5, immunoglobulin class switching, GC formation and ASC differentiation were impaired. Single-cell multi-omic sequencing analyses revealed that SMARCA5 is crucial for facilitating the transcriptional modifications and genomic accessibility of genes that support B cell differentiation. These findings offer novel insights into SMARCA5, which can be targeted in lymphoma patients. Overall design: CUT&RUN analysis of WT GC B cells from inguinal lymph nodes 7 days after immunization with KLH+CFA