The CXCR7 chemokine receptor promotes B-cell retention in the splenic marginal zone and serves as a sink for CXCL12

The splenic marginal zone (MZ) is comprised of specialized populations of B cells, dendritic cells, and macrophages that are uniquely arrayed outside the white pulp follicles to screen the blood for bacterial and other particulate Ags. Mechanisms responsible for MZ B-cell formation, localization, retention, and function are understood to include antigenic specificity, transcription factors, integrins, and surface receptors for soluble ligands such as S1P. Here, we add to this repertoire by demonstrating that the receptor for CXCL12, CXCR7, is expressed on MZ but not on follicular B cells. Treatment of mice with CXCR7 inhibitors led to disruption of MZ architecture, reduced numbers of MZ B cells, and altered granulocyte homeostasis associated with increasing serum levels of CXCL12. CXCR7 thus appears to function as a scavenger receptor for CXCL12 on MZ B cells. (Blood. 2012;119(2):465-468)