Sin1/mTORC2 regulate B cell growth and metabolism by activating mTORC1 and Myc  

作　　者：Man Li Adam S.Lazorchak Xinxing Ouyang Huihui Zhang Hongzhi Liu Omotooke A.Arojo Lichong Yan Jingsi Jin Yuheng Han Guojun Qu Yuhong Fu Xiaocao Xu Xiaobo Liu Wenqian Zhang Zhengfeng Yang Chuan Ruan Qijun Wang Dou Liu Chuanxin Huang Lu Lu Shibo Jiang Fubin Li Bing Su 

机构地区：[1]Shanghai Institute of Immunology,Department of Immunology and Microbiology,Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China [2]Department of Immunobiology and the Vascular Biology and Therapeutics Program,Yale University School of Medicine,333 Cedar Street,New Haven,Connecticut 06520,USA [3]Present address:EMD Serono Research&Development Institute,Inc.,45 Middlesex Tpke,Billerica,MA 01821–3936,USA [4]Hongqiao International Institute of Medicine,Shanghai Tongren Hospital and Faculty of Basic Medicine,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China [5]Shanghai Public Health Clinical Center and School of Basic Medical Sciences,Key Laboratory of Medical Molecular Virology of MOE/MOH,Fudan University,Shanghai,China

出　　处：《Cellular & Molecular Immunology》2019年第9期757-769,共13页中国免疫学杂志（英文版）

基　　金：This study was partially supported by grant PR093728(DoD to B.S.);the National Natural Science Foundation of China(grant numbers 31470845 and 81430033 to B.S.,31422020 to F.L.and 31600704 to H.H.Z.);grant 13JC1404700 from the Program of Science and Technology Commission of Shanghai Municipality(B.S.);the Ministry of Science and Technology of China(Program 2014CB943600,F.L.);Chinese Mega Project on Infectious Diseases(No.2018ZX10302301).

摘　　要：Proper control of B cell growth and metabolism is crucial for B-cell-mediated immunity,but the underlying molecular mechanisms remain incompletely understood.In this study,Sin1,a key component of mTOR complex 2(mTORC2),specifically regulates B cell growth and metabolism.Genetic ablation of Sin1 in B cells reduces the cell size at either the transitional stage or upon antigen stimulation and severely impairs metabolism.Sin1 deficiency also severely impairs B-cell proliferation,antibody responses,and anti-viral immunity.At the molecular level,Sin1 controls the expression and stability of the c-Myc protein and maintains the activity of mTORC1 through the Akt-dependent inactivation of GSK3 and TSC1/2,respectively.Therefore,our study reveals a novel and specific role for Sin1 in coordinating the activation of mTORC2 and mTORC1 to control B cell growth and metabolism.

关 键 词：METABOLISM IMMUNITY STIMULATION 

分 类 号：R73[医药卫生—肿瘤]