Brief Report: Defective Early B Cell Tolerance Checkpoints in Sjögren's Syndrome Patients

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.