Sjögren's disease (SjD) is a chronic autoimmune disorder characterized by increased circulating self-reactive B cells. While many of these self-reactive B cells emerge from the bone marrow, it is not known whether they are excluded from or enriched in specific developmental stages in the periphery. The aim of this study was to determine the immunophenotype of circulating self-reactive B cells in SjD to inform more precise therapeutic targeting. Five major B cell populations: transitional, mature naïve, switched memory, double negative and plasmablasts were single-cell sorted and cultured to produce IgG. Self-reactive IgG was identified by ELISA, flow cytometry of permeabilized HEK293 cells and HEp-2 indirect immunofluorescence. Immunoglobulin heavy chains were sequenced by Sanger and next-generation sequencing. Compared with healthy donor controls (HCs), SjD patients had higher frequencies of naïve and CD21