Autoreactive B cells in the peripheral blood of patients with Sjogren's syndrome

Abstract

Introduction: Sjogren's syndrome (SS) is an autoimmune disorder characterised by dryness, fatigue and serum autoantibodies to Ro/La (nuclear) ribonucleoproteins produced by autoreactive B cells. What causes B cells to become autoreactive, and the specific B cell developmental state where autoreactivity arises, is not clear; hence, we examined B cell populations in the blood for reactivity to nuclear/cellular antigens. Method(s): Blood from three seropositive SS patients were single cell-sorted for five B cell populations: transitional, naive, switched memory, IgD-CD27- double negative (DN) and plasmablast. Cells were cultured for 2 weeks. Supernatants were screened for autoantibodies using ELISA and flow cytometry of permeabilised human embryonic kidney cells. Result(s): Mean ranges of 23-50% (n=602) of sorted B cells produced detectable IgG. Plasmablast IgG were significantly higher than transitional and DN B cell populations. None of the detectable IgG demonstrated reactivity towards Ro52, Ro60 or La autoantigens. However, nuclear/cellular IgG autoreactivity was enriched in the transitional and DN B cells relative to other populations. Conclusion(s): Ro/La autoantibody-secreting cells are very rare or absent in the blood of patients with SS, suggesting sequestration at tissue sites. Autoreactive transitional and DN cells indicates escape of peripheral tolerance, for which future studies will address the mechanisms.Copyright 2023