The role of plexin-D1 in the adaptive immune system: Implications for humoral immunity

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.