Antibody-Independent Function of Human B Cells Contributes to Antifungal T Cell Responses
Antibody-Independent Function of Human B Cells Contributes to Antifungal T Cell Responses
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DOI：
10.4049/jimmunol.1601572
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发表时间：
2017-04-15
影响因子：
4.4
通讯作者：
Bar-Or, Amit
中科院分区：
文献类型：
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作者：
Li, Rui;Rezk, Ayman;Bar-Or, Amit
真菌感染(例如白色念珠菌)可表现为严重的医学疾病，特别是在老年人和免疫功能低下的宿主中。T细胞对念珠菌的控制很重要。B细胞是否以及如何参与抗真菌免疫还不是很清楚。尽管无丙种球蛋白血症患者表现出正常的抗真菌免疫，但据报道，B细胞耗尽治疗后真菌感染增加，共同表明B细胞在控制此类感染中发挥着非抗体依赖的作用。为了测试人类B细胞如何对真菌相关的人类T细胞反应做出贡献，我们开发了一种新型的Ag特异性人类T细胞/B细胞体外共培养系统，发现人类B细胞可以诱导白色念珠菌相关的、MHC II类限制性的初始T细胞反应。活化的B细胞显著增强白念珠菌介导的Th1和Th17T细胞应答，CD80/CD86共刺激强烈诱导Th1和Th17T细胞应答。IL-6(+)GM-CSF+B细胞是白念珠菌免疫应答的主要B细胞亚群，为T细胞提供有效的共刺激信号。在活体内，人类的B细胞耗尽导致白色念珠菌相关的T反应减少。值得注意的是，降低的Th17反应，而不是Th1，可以通过IL-6依赖的方式在耗尽前被B细胞的可溶性因子逆转。综上所述，我们的结果暗示了在人类抗真菌T细胞反应中，抗体不依赖的细胞因子定义的B细胞作用。考虑到慢性B细胞耗竭治疗在淋巴瘤和自身免疫性疾病中应用的前景，随着患者年龄的增长和接受一系列联合治疗，这些发现可能特别相关。
Fungal infections (e.g., Candida albicans) can manifest as serious medical illnesses, especially in the elderly and immune-compromised hosts. T cells are important for Candida control. Whether and how B cells are involved in antifungal immunity has been less clear. Although patients with agammaglobulinemia exhibit normal antifungal immunity, increased fungal infections are reported following B cell-depleting therapy, together pointing to Ab-independent roles of B cells in controlling such infections. To test how human B cells may contribute to fungal-associated human T cell responses, we developed a novel Ag-specific human T cell/B cell in vitro coculture system and found that human B cells could induce C. albicans-associated, MHC class II-restricted responses of naive T cells. Activated B cells significantly enhanced C. albicans-mediated Th1 and Th17 T cell responses, which were both strongly induced by CD80/CD86 costimulation. IL-6(+) GM-CSF+ B cells were the major responding B cell subpopulation to C. albicans and provided efficient costimulatory signals to the T cells. In vivo B cell depletion in humans resulted in reduced C. albicans-associated T responses. Of note, the decreased Th17, but not Th1, responses could be reversed by soluble factors from B cells prior to depletion, in an IL-6-dependent manner. Taken together, our results implicate an Ab-independent cytokine-defined B cell role in human antifungal T cell responses. These findings may be particularly relevant given the prospects of chronic B cell depletion therapy use in lymphoma and autoimmune disease, as patients age and are exposed to serial combination therapies.