CCL3 promotes germinal center B cells sampling by follicular regulatory T cells and ensures optimal humoral response

A hallmark of adaptive humoral immunity is formation of germinal centers (GC), the site of B cell antigen-dependent clonal expansion, immunoglobulin diversification, and affinity maturation. This set of coordinated processes is dependent on follicular T cells and leads to generation of memory cells and long-lived plasma cells that secrete high-affinity antibodies. Despite the wealth of studies dissecting the chemotactic cues that organize GCs, it is unclear whether GC B cells may secrete additional factors that enable their efficient sampling by follicular T cells. In this work we show that in mice a small subset of GC centrocytes upregulates expression of proinflammatory chemokines CCL3/4. We also demonstrate that GC B cells-intrinsic production of CCL3 promotes their direct interactions with follicular regulatory T cells (Tfr), but not follicular helper T cells (Tfh) in vivo . Finally, we show that GC B cells-intrinsic production of CCL3 is required for optimal control of GC responses.