B cell-reactive triad of B cells,follicular helper and regulatory T cells at homeostasis  

作　　者：Yihan Lin Zurong Wan Bo Liu Jiacheng Yao Tianqi Li Fang Yang Jianhua Sui Yongshan Zhao Wanli Liu Xuyu Zhou Jianbin Wang Hai Qi 

机构地区：[1]Tsinghua-Peking Center for Life Sciences,Beijing,China [2]Laboratory of Dynamic Immunobiology,Institute for Immunology,Tsinghua University,Beijing,China [3]Department of Basic Medical Sciences,School of Medicine,Tsinghua University,Beijing,China [4]Changping Laboratory,Beijing,China [5]School of Life Sciences,Tsinghua University,Beijing,China [6]National Institute of Biological Sciences,Beijing,China [7]Institute of Microbiology,Chinese Academy of Sciences,Beijing,China [8]New Cornerstone Science Laboratory,School of Medicine,Tsinghua University,Beijing,China [9]Beijing Key Laboratory for Immunological Research on Chronic Diseases,Tsinghua University,Beijing,China [10]Beijing Frontier Research Center for Biological Structure,Tsinghua University,Beijing,China [11]SXMU-Tsinghua Collaborative Innovation Center for Frontier Medicine,Shanxi Medical University,Taiyuan,Shanxi,China [12]Present address:Weill Cornell Medical College,Cornell University,Ithaca,NY,USA

出　　处：《Cell Research》2024年第4期295-308,共14页细胞研究（英文版）

基　　金：funded in part by the National Key R&D Program of China(Ministry of Science and Technology,2018YFE0200300 to H.Q.);the National Natural Science Foundation of China(32130037,81621002 to H.Q.);the Natural Science Foundation of Beijing(grant 5224040 to B.L.).

摘　　要：Autoreactive B cells are silenced through receptor editing,clonal deletion and anergy induction.Additional autoreactive B cells are ignorant because of physical segregation from their cognate autoantigen.Unexpectedly,we find that follicular B cell-derived autoantigen,including cell surface molecules such as FcγRIIB,is a class of homeostatic autoantigen that can induce spontaneous germinal centers(GCs)and B cell-reactive autoantibodies in non-autoimmune animals with intact T and B cell repertoires.These B cell-reactive B cells form GCs in a manner dependent on spontaneous follicular helper T(TFH)cells,which preferentially recognize B cell-derived autoantigen,and in a manner constrained by spontaneous follicular regulatory T(TFR)cells,which also carry specificities for B cell-derived autoantigen.B cell-reactive GC cells are continuously generated and,following immunization or infection,become intermixed with foreign antigen-induced GCs.Production of plasma cells and antibodies derived from B cell-reactive GC cells are markedly enhanced by viral infection,potentially increasing the chance for autoimmunity.Consequently,immune homeostasis in healthy animals not only involves classical tolerance of silencing and ignoring autoreactive B cells but also entails a reactive equilibrium attained by a spontaneous B cell-reactive triad of B cells,TFH cells and TFR cells.

关 键 词：HOMEOSTASIS markedly CENTERS 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]