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.

T细胞依赖性生发中心（GC）响应需要在存在B7和CD40依赖性共刺激途径的情况下，T细胞与两个抗原呈递细胞（APC）群体，B细胞和树突状细胞（DC）协同相互作用。 。与流行的范例相反，我们发现在用蛋白抗原和佐剂疫苗免疫的一级GC反应中，B7和CD40表达具有独特的细胞要求：DC上需要B7，但B细胞上不需要B7，而B40上需要CD40，但是在抗原特异性卵泡辅助性T细胞，抗原特异性GC B细胞和高亲和力类别转换抗体的产生中，DC的作用并不明显。实际上，在这些反应中，不需要在同一细胞上共表达B7和CD40。