| Plexin and semaphorin molecules direct axon localization by generating attractive and repulsive forces. Recently, plexin and semaphorin molecules have been shown to control cell movement and cell-cell interaction in the immune system. In this study, we characterize the expression and function of plexin-D1 in the immune system. We show that plexin-D1 is highly expressed in thymocyte, B cell and dendritic cell compartments. Absence of Plexin-D1 resulted in aberrant thymic development and impaired DP thymocyte migration from the cortex to the medulla. However, we found that absence of plexin-D1 did not affect the formation of mature T cell compartments and peripheral T cells were capable to respond to antigenic challenge. Normal B cell development and maturation was observed in PlxnD1-/- mice; however, these mice exhibited defective germinal center (GC) reactions during T-dependent immune activation. Protective humoral immune responses depend upon the generation of memory B cells and long-lived plasma cells formed in the GC reaction. We demonstrate that Plexin-D1 is responsible for migration of activated B cells into the GC. We correlate these observations with reduced migration of PlxnD1-/- B cells towards the GC chemokines, CXCL12, CXCL13 and CCL19. Accordingly, PlxnD1 -/- mice exhibited defective production of IgG1 and IgG2b, but not IgG3 serum antibody, accompanied by reductions in high-affinity antibody, long-lived bone marrow plasmacytes, and recall humoral memory response. These data show a new role for plexin molecules in the GC reaction and generation of immunologic memory. |
