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Brief Report: Defective Early B Cell Tolerance Checkpoints in Sjögren's Syndrome Patients
Author(s) -
Glauzy Salomé,
Sng Joel,
Bannock Jason M.,
Gottenberg JacquesEric,
Korganow AnneSophie,
Cacoub Patrice,
Saadoun David,
Meffre Eric
Publication year - 2017
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.40215
Subject(s) - autoimmunity , antibody , b cell , immunology , clone (java method) , peripheral tolerance , antigen , recombinant dna , biology , central tolerance , naive b cell , t cell , microbiology and biotechnology , antigen presenting cell , immune system , genetics , gene
Objective Central and peripheral B cell tolerance checkpoints are defective in many patients with autoimmune diseases, but the functionality of each discrete checkpoint has not been assessed in patients with Sjögren's syndrome ( SS ). We undertook this study to assess this functionality in SS patients. Methods Using a polymerase chain reaction–based approach that allows us to clone and express, in vitro, recombinant antibodies produced by single B cells, we tested the reactivity of recombinant antibodies cloned from single CD 19+ CD 21 low CD 10+IgM high CD 27– newly emigrant/transitional B cells and CD 19+ CD 21+ CD 10–IgM+ CD 27– mature naive B cells from 5 SS patients. Results We found that the frequencies of newly emigrant/transitional B cells expressing polyreactive antibodies were significantly increased in SS patients compared to those in healthy donors, revealing defective central B cell tolerance in SS patients. Frequencies of mature naive B cells expressing autoreactive antibodies were also significantly increased in SS patients, thereby illustrating an impaired peripheral B cell tolerance checkpoint in these patients. Conclusion Defective counterselection of developing autoreactive B cells observed in SS patients is a feature common to many other autoimmune diseases and may favor the development of autoimmunity by allowing autoreactive B cells to present self antigens to T cells.