A Germinal Center Checkpoint of AIRE in B Cells Limits Antibody Diversification
Year: 2026
Type: preprint
Abstract: In response to antigens, B cells undergo antibody diversification, including affinity maturation and class switching, mediated by activation-induced cytidine deaminase (AID) in secondary lymphoid organs, but uncontrolled AID activity can precipitate autoimmunity and cancer. The regulation of antibody diversification is of fundamental importance, though the mechanisms underlying these pathways are not well understood. We found that autoimmune regulator (AIRE), the molecule essential for T cell tolerance, is expressed in germinal center (GC) B cells in a CD40-dependent manner, interacts with AID and negatively regulates antibody affinity maturation and class switching by inhibiting AID function. AIRE deficiency in B cells caused altered antibody repertoire, increased somatic hypermutations, elevated autoantibodies to T helper 17 effector cytokines and defective control of skin Candida albicans. These results define a GC B cell checkpoint of humoral immunity and illuminate new approaches of generating high-affinity neutralizing antibodies for immunotherapy.
Source: eLife
Authors: Jordan Z Zhou, Bo Pei, Guang Wen Sun, Michael D Pawlitz, Wei Zhang, Xinyang Li, Fayi Yao, Kati C Hokynar, Chun-Xiao Li, Madusha LW Perera, Shanqiao Wei, Simin Zheng, Lisa A Polin, Janet M Poulik, Annamari Ranki, Kai Krohn, Charlotte Cunningham-Rundles, Andrea Cerutti, Naibo Yang, Ashok S Bhagwat, Kefei Yu, Pärt Peterson, Kai Kisand, Bao Q Vuong, Bihui Huang, Kang Chen
Institutions: Wayne State University, Weill Cornell Medicine, Republic Polytechnic, Central South University, Henan University of Urban Construction, University of Helsinki, Nanyang Technological University, The Barbara Ann Karmanos Cancer Institute, Children's Hospital of Michigan, Icahn School of Medicine at Mount Sinai, Hospital del Mar Research Institute, Michigan State University, University of Tartu, City College of New York, Sun Yat-sen University, National Institutes of Health, National Institute of Allergy and Infectious Diseases
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
OpenAlex ID: W7213878959