Division of Immunoregulation, Medical Research Council National Institute for Medical Research, The Ridgeway, London NW7 1AA, United Kingdom.
J Immunol. 2011 Sep 15;187(6):3321-30. doi: 10.4049/jimmunol.1101006. Epub 2011 Aug 12.
The T cell-dependent B cell response relies on cognate interaction between B cells and CD4(+) Th cells. However, the consequences of this interaction for CD4(+) T cells are not entirely known. B cells generally promote CD4(+) T cell responses to pathogens, albeit to a variable degree. In contrast, CD4(+) T cell responses to self- or tumor Ags are often suppressed by B cells. In this study, we demonstrated that interaction with B cells dramatically inhibited the function of virus-specific CD4(+) T cells in retroviral infection. We have used Friend virus infection of mice as a model for retroviral infection, in which the behavior of virus-specific CD4(+) T cells was monitored according to their TCR avidity. We report that avidity for Ag and interaction with B cells determine distinct aspects of the primary CD4(+) T cell response to Friend virus infection. Virus-specific CD4(+) T cells followed exclusive Th1 and T follicular helper (Tfh) differentiation. High avidity for Ag facilitated expansion during priming and enhanced the capacity for IFN-γ and IL-21 production. In contrast, Tfh differentiation was not affected by avidity for Ag. By reducing or preventing B cell interaction, we found that B cells promoted Tfh differentiation, induced programmed death 1 expression, and inhibited IFN-γ production by virus-specific CD4(+) T cells. Ultimately, B cells protected hosts from CD4(+) T cell-mediated immune pathology, at the detriment of CD4(+) T cell-mediated protective immunity. Our results suggest that B cell presentation of vaccine Ags could be manipulated to direct the appropriate CD4(+) T cell response.
T 细胞依赖性 B 细胞反应依赖于 B 细胞和 CD4(+) Th 细胞之间的同源相互作用。然而，这种相互作用对 CD4(+) T 细胞的后果并不完全清楚。B 细胞通常促进 CD4(+) T 细胞对病原体的反应，但程度不同。相比之下，CD4(+) T 细胞对自身或肿瘤抗原的反应通常被 B 细胞抑制。在这项研究中，我们证明了与 B 细胞的相互作用极大地抑制了逆转录病毒感染中病毒特异性 CD4(+) T 细胞的功能。我们使用 Friend 病毒感染小鼠作为逆转录病毒感染的模型，根据其 TCR 亲和力来监测病毒特异性 CD4(+) T 细胞的行为。我们报告称，抗原亲和力和与 B 细胞的相互作用决定了 Friend 病毒感染中初始 CD4(+) T 细胞反应的不同方面。病毒特异性 CD4(+) T 细胞遵循独特的 Th1 和滤泡辅助性 T 细胞（Tfh）分化。高抗原亲和力有助于在启动时扩增，并增强 IFN-γ 和 IL-21 的产生能力。相比之下，抗原亲和力对 Tfh 分化没有影响。通过减少或防止 B 细胞相互作用，我们发现 B 细胞促进了 Tfh 分化，诱导程序性死亡 1 表达，并抑制了病毒特异性 CD4(+) T 细胞的 IFN-γ 产生。最终，B 细胞保护宿主免受 CD4(+) T 细胞介导的免疫病理学，牺牲了 CD4(+) T 细胞介导的保护性免疫。我们的结果表明，B 细胞呈递疫苗抗原可以被操纵以引导适当的 CD4(+) T 细胞反应。
