B cell abnormalities and autoantibody production in patients with partial RAG deficiency

Frontiers in Immunology

Immunology

Meiping Yu¹  Qing Min¹  Ji-Yang Wang²  Lulu Dong³  Xin Meng³  Yaxuan Li³  Ziying Hu⁴  Krisztian Csomos⁵  Jolan E. Walter⁶ 

[1] Department of Clinical Immunology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, China;Department of Clinical Immunology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, China;Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China;Department of Microbiology and Immunology, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China;Shanghai Huashen Institute of Microbes and Infections, Shanghai, China;Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China;Department of Microbiology and Immunology, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China;Division of Pediatric Allergy/Immunology, University of South Florida at Johns Hopkins All Children’s Hospital, St. Petersburg, FL, United States;Division of Pediatric Allergy/Immunology, University of South Florida at Johns Hopkins All Children’s Hospital, St. Petersburg, FL, United States;Division of Pediatric Allergy/Immunology, Massachusetts General Hospital for Children, Boston, MA, United States;

关键词: RAG deficiency;    B cell tolerance;    BAFF;    homeostatic proliferation;    double negative B;    CD11cTbet B;    autoantibody production;   

DOI  :  10.3389/fimmu.2023.1155380

 received in 2023-01-31, accepted in 2023-06-15,  发布年份 2023

来源: Frontiers

【 摘 要 】

Mutations in the recombination activating gene 1 (RAG1) and RAG2 in humans are associated with a broad spectrum of clinical phenotypes, from severe combined immunodeficiency to immune dysregulation. Partial (hypomorphic) RAG deficiency (pRD) in particular, frequently leads to hyperinflammation and autoimmunity, with several underlying intrinsic and extrinsic mechanisms causing a break in tolerance centrally and peripherally during T and B cell development. However, the relative contributions of these processes to immune dysregulation remain unclear. In this review, we specifically focus on the recently described tolerance break and B cell abnormalities, as well as consequent molecular and cellular mechanisms of autoantibody production in patients with pRD.

【 授权许可】

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Copyright © 2023 Min, Csomos, Li, Dong, Hu, Meng, Yu, Walter and Wang