气候变化领域集成服务门户(CCPortal): An autoimmune disease variant of IgG1 modulates B cell activation and differentiation

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DOI	10.1126/science.aap9310
	An autoimmune disease variant of IgG1 modulates B cell activation and differentiation
	Chen X.; Sun X.; Yang W.; Yang B.; Zhao X.; Chen S.; He L.; Chen H.; Yang C.; Xiao L.; Chang Z.; Guo J.; He J.; Zhang F.; Zheng F.; Hu Z.; Yang Z.; Lou J.; Zheng W.; Qi H.; Xu C.; Zhang H.; Shan H.; Zhou X.-J.; Wang Q.; Shi Y.; Lai L.; Li Z.; Liu W.
发表日期	2018
ISSN	0036-8075
起始页码	700
结束页码	705
卷号	362 期号:6415
英文摘要	The maintenance of autoreactive B cells in a quiescent state is crucial for preventing autoimmunity. Here we identify a variant of human immunoglobulin G1 (IgG1) with a Gly 396 →Arg substitution (hIgG1-G396R), which positively correlates with systemic lupus erythematosus. In induced lupus models, murine homolog Gly 390 →Arg (G390R) knockin mice generate excessive numbers of plasma cells, leading to a burst of broad-spectrum autoantibodies. This enhanced production of antibodies is also observed in hapten-immunized G390R mice, as well as in influenza-vaccinated human G396R homozygous carriers. This variant potentiates the phosphorylation of the IgG1 immunoglobulin tail tyrosine (ITT) motif. This, in turn, alters the availability of phospho-ITT to trigger longer adaptor protein Grb2 dwell times in immunological synapses, leading to hyper–Grb2–Bruton’s tyrosine kinase (Btk) signaling upon antigen binding. Thus, the hIgG1-G396R variant is important for both lupus pathogenesis and antibody responses after vaccination. © 2018 American Association for the Advancement of Science. All rights reserved.
英文关键词	arginine; autoantibody; Bruton tyrosine kinase; glycine; growth factor receptor bound protein 2; immunoglobulin G1; influenza vaccine; protein variant; tyrosine; arginine; autoantibody; glycine; Grb2 protein, mouse; growth factor receptor bound protein 2; immunoglobulin G; antibody; antigen; biotechnology; cell; disease incidence; immune response; rodent; vaccination; amino acid substitution; antibody production; antibody response; antigen binding; Article; autoimmune disease; autoimmunity; B lymphocyte activation; cell count; homozygote; human; immunopathogenesis; influenza; influenza vaccination; lymphocyte differentiation; nonhuman; plasma cell; priority journal; protein motif; protein phosphorylation; relapse; sequence homology; signal transduction; systemic lupus erythematosus; animal; B lymphocyte; biosynthesis; C57BL mouse; cell differentiation; disease model; gene knock-in; genetics; heterozygote; immunological synapse; immunology; lymphocyte activation; mouse; phosphorylation; systemic lupus erythematosus; Murinae; Mus; Amino Acid Substitution; Animals; Arginine; Autoantibodies; Autoimmunity; B-Lymphocytes; Cell Differentiation; Disease Models, Animal; Gene Knock-In Techniques; Glycine; GRB2 Adaptor Protein; Heterozygote; Humans; Immunoglobulin G; Immunological Synapses; Lupus Erythematosus, Systemic; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Phosphorylation; Plasma Cells; Signal Transduction
语种	英语
来源期刊	Science
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/243305
作者单位	Ministry of Education Key Laboratory of Protein Sciences, Center for Life Sciences, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Institute for Immunology, School of Life Sciences, Tsinghua University, Beijing, 100084, China; Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing Key Laboratory for Rheumatism and Immune Diagnosis (BZ0135), Peking-Tsinghua Center for Life Sciences, State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100044, China; School of Life Sciences, Tsinghua University, Beijing, 100084, China; Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China; Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China; Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Department...
推荐引用方式 GB/T 7714	Chen X.,Sun X.,Yang W.,et al. An autoimmune disease variant of IgG1 modulates B cell activation and differentiation[J],2018,362(6415).
APA	Chen X..,Sun X..,Yang W..,Yang B..,Zhao X..,...&Liu W..(2018).An autoimmune disease variant of IgG1 modulates B cell activation and differentiation.Science,362(6415).
MLA	Chen X.,et al."An autoimmune disease variant of IgG1 modulates B cell activation and differentiation".Science 362.6415(2018).