Co-stimulatory function in primary germinal center responses: CD40 and B7 are required on distinct antigen-presenting cells

Watanabe et al. report that, contrary to the prevailing paradigm, there are unique cellular requirements for B7 and CD40 expression in primary GC responses. B7 is required on DCs but not on B cells, whereas CD40 is required on B cells but not on DCs for generation of Tfh cells, GC B cells, and high-affinity class-switched antibody production.
T cell–dependent germinal center (GC) responses require coordinated interactions of T cells with two antigen-presenting cell (APC) populations, B cells and dendritic cells (DCs), in the presence of B7- and CD40-dependent co-stimulatory pathways. Contrary to the prevailing paradigm, we found unique cellular requirements for B7 and CD40 expression in primary GC responses to vaccine immunization with protein antigen and adjuvant: B7 was required on DCs but was not required on B cells, whereas CD40 was required on B cells but not on DCs in the generation of antigen-specific follicular helper T cells, antigen-specific GC B cells, and high-affinity class-switched antibody production. There was, in fact, no requirement for coexpression of B7 and CD40 on the same cell in these responses. Our findings support a substantially revised model for co-stimulatory function in the primary GC response, with crucial and distinct contributions of B7- and CD40-dependent pathways expressed by different APC populations and with important implications for understanding how to optimize vaccine responses or limit autoimmunity.