Molecular and cellular phenotype of self-reactive B cells in Sjogren's disease

Abstract

INTRODUCTION: Sjogren's disease (SjD) is an autoimmune disease that causes widespread pain, fatigue and dryness symptoms of the eyes and mouth. Pathologically, it is characterised by B cell hyperreactivity, self-reactivity and autoantibodies to nuclear autoantigens. The specific B cell developmental state where self-reactivity arises, is not clear and identifying circulating self-reactive B cells would inform targeted therapy. Hence, we examined five populations within the peripheral blood B cell compartment of patients with SjD for reactivity to nuclear/cellular antigens. METHODS: We performed flow cytometry to compare B cells across SjD patients and healthy donors. Five blood B cell populations: transitional, mature naive, switched memory, double negative and plasmablasts from 5 SjD patients were single cell-sorted and cultured for two weeks. Supernatants were assessed for self-reactivity using ELISA and flow cytometry of permeabilised HEK293 cells. RESULTS: Early (antigen-inexperienced) B cells were expanded in the blood of SjD patients and displayed evidence for high self-reactivity compared to corresponding populations in healthy donors. CONCLUSIONS: Consistent with their autoimmune diathesis, a greater degree of nuclear/cellular self-reactivity was seen in the circulating B cell populations of SjD patients.