Department of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland.
J Immunol. 2013 Sep 1;191(5):2344-50. doi: 10.4049/jimmunol.1300643. Epub 2013 Aug 5.
Follicular helper T (TFH) cells are specialized in providing help for B cell differentiation and Ab secretion. Several positive and negative regulators of TFH cell differentiation have been described but their control is not fully understood. In this study, we show that Notch signaling in T cells is a major player in the development and function of TFH cells. T cell-specific gene ablation of Notch1 and Notch2 impaired differentiation of TFH cells in draining lymph nodes of mice immunized with T-dependent Ags or infected with parasites. Impaired TFH cell differentiation correlated with deficient germinal center development and the absence of high-affinity Abs. The impact of loss of Notch on TFH cell differentiation was largely independent of its effect on IL-4. These results show a previously unknown role for Notch in the regulation of TFH cell differentiation and function with implications for the control of this T cell population.
滤泡辅助 T（TFH）细胞专门为 B 细胞分化和 Ab 分泌提供帮助。已经描述了几种 TFH 细胞分化的正性和负性调节因子，但它们的调控尚不完全清楚。在这项研究中，我们表明 T 细胞中的 Notch 信号是 TFH 细胞发育和功能的主要参与者。在用 T 依赖性抗原免疫或寄生虫感染的小鼠中，T 细胞特异性 Notch1 和 Notch2 的基因缺失会损害引流淋巴结中 TFH 细胞的分化。TFH 细胞分化受损与生发中心发育缺陷和缺乏高亲和力 Ab 相关。Notch 缺失对 TFH 细胞分化的影响在很大程度上与其对 IL-4 的影响无关。这些结果表明 Notch 在调节 TFH 细胞分化和功能方面具有先前未知的作用，这对控制这种 T 细胞群体具有重要意义。
