Yang Jialong, Lin Xingguang, Pan Yun, Wang Jinli, Chen Pengcheng, Huang Hongxiang, Xue Hai-Hui, Gao Jimin, Zhong Xiao-Ping
Department of Pediatrics, Division of Allergy and Immunology, Duke University Medical Center, Durham, United States.
School of Laboratory Medicine, Wenzhou Medical University, Wenzhou, China.
Elife. 2016 Sep 30;5:e17936. doi: 10.7554/eLife.17936.
T follicular helper (Tfh) cells play critical roles for germinal center responses and effective humoral immunity. We report here that mTOR in CD4 T cells is essential for Tfh differentiation. In mice, both constitutive and inducible Tfh differentiation is severely impaired, leading to defective germinal center B cell formation and antibody production. Moreover, both mTORC1 and mTORC2 contribute to Tfh and GC B cell development but may do so via distinct mechanisms. mTORC1 mainly promotes CD4 T cell proliferation to reach the cell divisions necessary for Tfh differentiation, while Rictor/mTORC2 regulates Tfh differentiation by promoting Akt activation and TCF1 expression without grossly influencing T cell proliferation. Together, our results reveal crucial but distinct roles for mTORC1 and mTORC2 in CD4 T cells during Tfh differentiation and germinal center responses.
滤泡辅助性T（Tfh）细胞在生发中心反应和有效的体液免疫中发挥着关键作用。我们在此报告，CD4 T细胞中的mTOR对Tfh分化至关重要。在小鼠中，组成型和诱导型Tfh分化均严重受损，导致生发中心B细胞形成和抗体产生存在缺陷。此外，mTORC1和mTORC2都有助于Tfh和生发中心B细胞的发育，但可能通过不同的机制发挥作用。mTORC1主要促进CD4 T细胞增殖，以达到Tfh分化所需的细胞分裂次数，而Rictor/mTORC2通过促进Akt激活和TCF1表达来调节Tfh分化，而不会对T细胞增殖产生显著影响。总之，我们的结果揭示了mTORC1和mTORC2在Tfh分化和生发中心反应过程中在CD4 T细胞中起着关键但不同的作用。
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