An autoimmune disease variant of IgG1 modulates B cell activation and differentiation-Reference-Cited by-同舟云学术

An autoimmune disease variant of IgG1 modulates B cell activation and differentiation

Published:2018-11-09 Issue:6415 Volume:362 Page:700-705
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Chen Xiangjun¹^ORCID,Sun Xiaolin²,Yang Wei³^ORCID,Yang Bing¹,Zhao Xiaozhen²^ORCID,Chen Shuting¹,He Lili¹,Chen Hui⁴,Yang Changmei¹,Xiao Le¹^ORCID,Chang Zai³,Guo Jianping²,He Jing²^ORCID,Zhang Fuping⁵,Zheng Fang⁶,Hu Zhibin⁷,Yang Zhiyong⁸^ORCID,Lou Jizhong⁴^ORCID,Zheng Wenjie⁹,Qi Hai¹⁰^ORCID,Xu Chenqi¹¹^ORCID,Zhang Hong¹²,Shan Hongying¹³^ORCID,Zhou Xu-jie¹²^ORCID,Wang Qingwen¹³^ORCID,Shi Yi¹⁴¹⁵^ORCID,Lai Luhua¹⁶^ORCID,Li Zhanguo²^ORCID,Liu Wanli¹¹⁷^ORCID

Affiliation:

1. 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.

2. 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.

3. School of Life Sciences, Tsinghua University, Beijing 100084, China.

4. Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.

5. Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.

6. Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

7. Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China.

8. Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA.

9. Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.

10. Tsinghua-Peking Center for Life Sciences, Laboratory of Dynamic Immunobiology, School of Medicine, Tsinghua University, Beijing 100084, China.

11. State Key Laboratory of Molecular Biology, Shanghai Science Research Center, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China.

12. Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, China.

13. Department of Rheumatism and Immunology, Peking University Shenzhen Hospital, Shenzhen 518036, China.

14. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing 100101, China.

15. Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China.

16. BNLMS, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, and Peking-Tsinghua Center for Life Sciences at College of Chemistry and Molecular Engineering, Center for Quantitative Biology, Peking University, Beijing 100871, China.

17. Beijing Key Lab for Immunological Research on Chronic Diseases, Beijing 100084, China.

Abstract

An IgG1 SNP enhances autoimmunity One common feature of autoimmune diseases like systemic lupus erythematosus (SLE) is the presence of high titers of self-reactive antibodies. These result in immune complexes, inflammation, and tissue pathology. Consequently, the checkpoints that normally keep immunoglobulin G (IgG)–positive autoreactive B cells in check are of intense interest. Chen et al. report the presence of a common IgG1 single-nucleotide polymorphism (SNP) in East Asian populations (hIgG1-G396R). This SNP was enriched in SLE patients and associated with increased disease severity. Humans with this SNP, as well as knockin mice, showed enhanced plasma cell accumulation and antibody production. This SNP enhanced IgG1 immunoglobulin tail tyrosine motif phosphorylation, triggering longer adaptor protein Grb2 dwell times in immunological synapses and hyper–Grb2–Bruton's tyrosine kinase signaling after antigen binding. Science , this issue p. 700

Funder

Beijing Nova Program

Ministry of Science and Technology of China

National Science Foundation China

Beijing Sci-Tech Program

Sanming Project of Medicine in Shenzhen

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference27 articles.

1. Pathogenic Roles of B Cells in Human Autoimmunity