Author: Aoun, Mike; Coelho, Ana; Krämer, Alexander; Saxena, Amit; Sabatier, Pierre; Beusch, Christian Michel; Lönnblom, Erik; Geng, Manman; Do, Nhu-Nguyen; Xu, Zhongwei; Zhang, Jingdian; He, Yibo; Romero Castillo, Laura; Abolhassani, Hassan; Xu, Bingze; Viljanen, Johan; Rorbach, Joanna; Fernandez Lahore, Gonzalo; Gjertsson, Inger; Kastbom, Alf; Sjöwall, Christopher; Kihlberg, Jan; Zubarev, Roman A; Burkhardt, Harald; Holmdahl, Rikard
Department: Inst för medicinsk biokemi och biofysik / Dept of Medical Biochemistry and Biophysics
Abstract
B cells undergo several rounds of selection to eliminate potentially pathogenic autoreactive clones, but in contrast to T cells, evidence of positive selection of autoreactive B cells remains moot. Using unique tetramers, we traced natural autoreactive B cells (C1-B) specific for a defined triple-helical epitope on collagen type-II (COL2), constituting a sizeable fraction of the physiological B cell repertoire in mice, rats, and humans. Adoptive transfer of C1-B suppressed arthritis independently of IL10, separating them from IL10-secreting regulatory B cells. Single-cell sequencing revealed an antigen processing and presentation signature, including induced expression of CD72 and CCR7 as surface markers. C1-B presented COL2 to T cells and induced the expansion of regulatory T cells in a contact-dependent manner. CD72 blockade impeded this effect suggesting a new downstream suppressor mechanism that regulates antigen-specific T cell tolerization. Thus, our results indicate that autoreactive antigen-specific naïve B cells tolerize infiltrating T cells against self-antigens to impede the development of tissue-specific autoimmune inflammation.
Institution:
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Division of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Solna, Sweden
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Division of Physiological Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Solna, Sweden
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Precision Medicine Institute, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
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Fraunhofer Institute for Translational Medicine and Pharmacology, and Fraunhofer Cluster of Excellence for Immune-Mediated Diseases , Frankfurt am Main, Germany
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Max Planck Institute Biology of Ageing-Karolinska Institute Laboratory, Karolinska Institute, Solna, Sweden
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Division of Molecular Metabolism, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Solna, Sweden
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Division of Clinical Immunology, Department of Biosciences and Nutrition, Karolinska Institutet, Karolinska University Hospital, Neo Building, Solna, Sweden
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Department of Chemistry, Biomedical Center, Uppsala University, Uppsala, Sweden
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Department of Rheumatology and Inflammation Research, University of Gothenburg, Gothenburg, Sweden
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Division of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
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Department of Pharmacological and Technological Chemistry, I.M. Sechenov First Moscow State Medical University, Moscow, Russia
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Division of Rheumatology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany
Citation: J Exp Med. 2023 Nov 6;220(11):e20230101.
Publishing journal: The Journal of experimental medicine
Eprint status: Peer Reviewed
Version: Published
Issue date: 2024-02-08
Sponsorship:
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Knut och Alice Wallenbergs Stiftelse (2019.0059)
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Vetenskapsrådet (2019-01209)
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Stiftelsen Konung Gustaf V:s 80-årsfond and Karolinska Institutet Foundation Grants for Rheumatology Research 2021 (SGI-2022-0862 and 2022-02852)
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HORIZON EUROPE Marie Sklodowska-Curie Actions (765158)
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Bundesministerium fur Bildung und Forschung (project 4 01 EC1009C)
Rights:
CC BY-NC-SA 4.0
Publication year: 2023