Early CCR6 expression on B cells modulates germinal centre kinetics and efficient antibody responses

Abstract

The CC-chemokine receptor 6 (CCR6) can be detected on naïve and activated B cells. Counterintuitively, its absence accelerates the appearance of germinal centres (GC) and increases the production of low-affinity antibodies. The detailed mechanism of CCR6 function during the humoral response has remained elusive but previously we identified a distinct CCR6(high) B cell population in vivo early after antigenic challenge. In this study, we defined this population specifically as early, activated pre-GC B cells. In accordance, we show that CCR6 is up-regulated rapidly within hours on protein or mRNA level after activation in vitro. Additionally, only activated B cells migrated specifically towards CCL20, the specific ligand for CCR6. Lack of CCR6 increased the dark zone/light zone ratio of GC and led to decreased antigen-specific IgG1 and IgG2a antibody generation in a B cell intrinsic manner in mixed bone marrow chimeras. In contrast, antigen-specific IgM responses were normal. Hence, CCR6 negatively regulates entry of activated, antigen-specific pre-GC B cells into the GC reaction.