IL 17 superfamily cytokines modulate normal germinal center B cell migration
The germinal center (GC) is a dynamic structure formed by proliferating B cells in the follicles of secondary lymphoid organs during T cell dependent antibody responses to exogenous antigens. GC is composed by a dark zone, enriched in proliferating centroblasts (CBs) and a light zone where CBs migrate and transform into centrocytes (CCs) a minority of which is selected to survive, undergoes Ig class switch recombination, and differentiates into memory B cells or long lived plasma cells. CBs express CXCR4 and are attracted to the dark zone by stromal cell derived CXCL12, whereas CCs express CXCR5 and are recruited to the light zone along a gradient of CXCL13 produced by follicular dendritic cells (FDCs) Therefore, CXCL12 and CXCL13 play crucial roles in the regulation of GC B cell trafficking. Among the numerous molecules involved in GC formation, IL 17A represents a recent addition. Its involvement has been demonstrated in mouse models of human autoimmune or infectious diseases. IL 17A belongs to the IL 17 cytokine superfamily, together with 5 additional structurally related cytokines. We have recently demonstrated that IL 17A renders freshly isolated tonsil GC B cells competent to migrate to CXCL12 and CXCL13 through a NF kBp65 dependent mechanism. Here, we review the role of IL 17A on GC cells and discuss, for the first time, common effects of the cognate cytokines IL 25 and IL 17B on GC B cell function.
Journal of leukocyte biology