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, using ribosomal pull-down for analyzing translated genes in GC B cells, coupled with functional experiments in mice, we identified SMARCA5 as a key chromatin remodeler in B cells. While the naive B cell compartment remained unaffected following conditional depletion of Smarca5, effective proliferation during B cell activation, immunoglobulin class switching, and as a result GC formation and ASC differentiation were impaired. Single-cell multiomic sequencing analyses revealed that SMARCA5 is crucial for facilitating the transcriptional modifications and genomic accessibility of genes that support B cell activation and differentiation. These findings offer novel insights into the functions of SMARCA5, which can be targeted in various human pathologies.

BIOCEV 1st Faculty of Medicine Charles University Vestec Czech Republic

Department of Chemical and Structural Biology Weizmann Institute of Science Rehovot Israel

Department of Immunology and Regenerative Biology Weizmann Institute of Science Rehovot Israel

Department of Systems Immunology Weizmann Institute of Science Rehovot Israel

Mantoux Bioinformatics Institute of the Nancy and Stephen Grand Israel National Center for Personalized Medicine Weizmann Institute of Science Rehovot Israel

The Crown Genomics Institute of the Nancy and Stephen Grand Israel National Center for Personalized Medicine Weizmann Institute of Science Rehovot Israel

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