Watanabe Masashi, Fujihara Chiharu, Radtke Andrea J, Chiang Y Jeffrey, Bhatia Sumeena, Germain Ronald N, Hodes Richard J
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
J Exp Med. 2017 Sep 4;214(9):2795-2810. doi: 10.1084/jem.20161955. Epub 2017 Aug 2.
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）反应需要T细胞与两种抗原呈递细胞（APC）群体，即B细胞和树突状细胞（DC），在B7和CD40依赖性共刺激途径存在的情况下进行协调相互作用。与普遍的模式相反，我们发现在用蛋白质抗原和佐剂进行疫苗免疫的原发性GC反应中，B7和CD40表达有独特的细胞需求：在产生抗原特异性滤泡辅助性T细胞、抗原特异性GC B细胞和高亲和力类别转换抗体时，DC上需要B7，但B细胞上不需要；而B细胞上需要CD40，DC上不需要。事实上，在这些反应中，同一细胞上不需要同时表达B7和CD40。我们的研究结果支持了一个关于原发性GC反应中共刺激功能的大幅修订模型，不同APC群体表达的B7和CD40依赖性途径有关键且不同的作用，这对于理解如何优化疫苗反应或限制自身免疫具有重要意义。
