First Author | Watanabe M | Year | 2017 |
Journal | J Exp Med | Volume | 214 |
Issue | 9 | Pages | 2795-2810 |
PubMed ID | 28768709 | Mgi Jnum | J:244030 |
Mgi Id | MGI:5912809 | Doi | 10.1084/jem.20161955 |
Citation | Watanabe M, et al. (2017) Co-stimulatory function in primary germinal center responses: CD40 and B7 are required on distinct antigen-presenting cells. J Exp Med 214(9):2795-2810 |
abstractText | 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. |