Defective Early B Cell Tolerance Checkpoints in Sjögren's Syndrome Patients.

Abstract

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. Using a polymerase chain reaction-based approach that allows us to clone and express, invitro, recombinant antibodies produced by single B cells, we tested the reactivity of recombinant antibodies cloned from single CD19+CD21low CD10+IgMhigh CD27- newly emigrant/transitional B cells and CD19+CD21+CD10-IgM+CD27- mature naive B cells from 5 SS patients. 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. 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.