The Role Of H3k36me2 Methyltransferase Nsd2 In Promoting Germinal Center Selection

The germinal center(GC)is the site where activated B cells undergo rapid expansions,somatic hypermutation,and affinity maturation.Cell expansion provides suffificient quantity of GC B cells and antibodies,whereas somatic hypermutation and affinity maturation improve the quality of antibodies.Antibody affinity maturation is an antigen-based selection process for B cells.During this process,GCB cells must efficiently recognize,acquire and present antigens from follicular dendritic cells(FDCs)to receive positive selection signals from T helper cells.Previous studies showed that GCB cells undergo adhesive interactions with FDCs in vitro,but the regulatory mechanisms underlying the cell adhesions and their functional relevance remain unclear.Here,we identified H3K36me2 methyltransferase Nsd2 as a critical regulator of GCB cell-FDC adhesion.Nsd2 deletion modestly reduced GC responses but strongly impaired B cell affinity maturation.Mechanistically,Nsd2 directly regulated expression of multiple actin polymerization-related genes in GCB cells.Nsd2 loss reduced B cell adhesion to FDC-expressed adhesion molecules,thus affecting both B cell receptor(BCR)signaling and antigen acquisition.Overall,Nsd2 coordinates GCB positive selection by enhancing both BCR signaling and T cell help.