Distinct and overlapping roles of CXCR5 and CCR7 in B-1 cell homing and early immunity against bacterial pathogens

Abstract: CXC chemokine receptor (CXCR)5 and chemokine receptor (CCR)7 are the major chemo-kine receptors required for B cell homing and microenvironmental localization during antigen-in-dependent and-dependent B cell differentiation. Here, we show markedly decreased B-1 B cell numbers in the peritoneal cavity of CXCR5/ and CXCR5/CCR7/ double-deficient mice paral-leled by reduced antigen-induced phosphorylcho-line-specific immunoglobulin (Ig)M responses after intraperitoneal (i.p.) administration of streprococ-cal antigen. CCR7/ mice also revealed a partial reduction in peritoneal B-1 cell numbers combined with a reduced humoral response to i.p.-injected bacterial antigen. However, opposite roles of CXCR5 and CCR7 were observed when the fre-quency of peritoneal B-2 cells was analyzed. CXCR5/ mice almost completely lacked B-2 cells, whereas CCR7 deficiency engendered an in-crease in peritoneal B-2 cells. In addition, CCR7/ mice had enhanced, splenic IgM plasma cell responses, whereas the extrafollicular B cell response of the CXCR5/mice was not signifi-cantly altered compared with wild-type controls. Thus, the two chemokine receptors exert divergent forces at multiple levels of the innate immune re-sponse. CXCR5 plays a dominant role in peritoneal B-1 B cell homing and body cavity immunity, but both chemokine receptors are needed for a pro-portional peritoneal B-2 cell homing and balanced development of an early splenic B cell response. J