Kumamoto Yosuke, Hirai Toshiro, Wong Patrick W, Kaplan Daniel H, Iwasaki Akiko
Department of Immunobiology, Yale University School of Medicine, New Haven, United States.
Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, United States.
Elife. 2016 Sep 22;5:e17979. doi: 10.7554/eLife.17979.
Strong antibody response is considered a hallmark of a successful vaccine. While dendritic cells (DCs) are important for T follicular helper (Tfh) cell priming, how this process is regulated in vivo is unclear. We show here that the depletion of CD301b DCs specifically enhanced the development of Tfh cells, germinal center B cells and antibody responses against protein antigens. Exaggerated antibody responses in mice depleted of CD301b DCs occurred in the absence of any adjuvants, and resulting antibodies had broader specificity and higher affinity to the immunogen. CD301b DCs express high levels of PD-1 ligands, PD-L1 and PD-L2. Blocking PD-1 or PD-L1 during priming in wild-type mice partially mimicked the phenotype of CD301b DC-depleted animals, suggesting their role in Tfh suppression. Transient depletion of CD301b DC results in the generation of autoreactive IgG responses. These results revealed a novel regulatory mechanism and a key role of CD301b DCs in blocking autoantibody generation.
强烈的抗体反应被认为是成功疫苗的一个标志。虽然树突状细胞（DCs）对于滤泡辅助性T（Tfh）细胞的启动很重要，但这一过程在体内是如何被调节的尚不清楚。我们在此表明，CD301b DCs的缺失特异性地增强了Tfh细胞、生发中心B细胞的发育以及针对蛋白质抗原的抗体反应。在没有任何佐剂的情况下，CD301b DCs缺失的小鼠中出现了过度的抗体反应，并且产生的抗体对免疫原具有更广泛的特异性和更高的亲和力。CD301b DCs高水平表达PD-1配体PD-L1和PD-L2。在野生型小鼠启动过程中阻断PD-1或PD-L1部分模拟了CD301b DCs缺失动物的表型，表明它们在抑制Tfh中的作用。CD301b DCs的短暂缺失导致自身反应性IgG反应的产生。这些结果揭示了一种新的调节机制以及CD301b DCs在阻断自身抗体产生中的关键作用。
