Publications

Abstract

Migration of B cells within lymphoid follicles is controlled by the chemokine receptors CXCR5 and CCR7 and the orphan G-protein-coupled receptor EBI2 (GPR183). Whilst CXCR5 and CCR7 are known to mediate migration towards their respective chemokine ligands, it is unclear whether EBI2 acts by modulating these processes or by directly mediating chemotaxis towards its own spatially restricted ligand. It is also unknown how signals from these three receptors are integrated to control B cell localization. To answer these questions, we generated compound knockout mice deficient in expression of EBI2, CXCR5 and/or CCR7. Analysis of these mice revealed that EBI2 directly mediates B cell migration towards the outer areas of follicles and to bridging channels of the spleen independent of both CXCR5 and CCR7. Thus, EBI2-mediated chemotaxis provides a third dimension to B cell migration that balances and integrates with the inputs from CXCR5 and CCR7 to determine B cell positioning. Migratory signals delivered by EBI2 were shown to control B cell organization within the spleen and to be particularly important for positioning activated B cells in the early stages of antibody responses. An additional minor role for EBI2 was identified in the organization and affinity maturation of B cells in the germinal center.