Diminished peripheral blood memory B cells and accumulation of memory B cells in the salivary glands of patients with Sjögren's syndrome

Abstract

Objective To delineate the mechanism of the abnormalities in B cell biology found in patients with primary Sjögren's syndrome (SS). Methods The distribution of peripheral B cell subpopulations in 21 patients with primary SS was analyzed by immunofluorescence labeling and flow cytometry. Immunoglobulin rearrangements were analyzed in single B cells isolated from the peripheral blood and parotid glands by fluorescence‐activated cell sorting. Results A significant reduction in the number of peripheral CD27+ memory B cells was found in SS patients, including a significantly reduced number of CD27+/IgD+/IgM+/CD5+ memory B cells. Remarkably, SS patients with secondary lymphoma uniquely exhibited an increase in CD27‐expressing peripheral B cells, including CD27^high plasmablasts. Molecular analysis for mutated Ig gene rearrangements confirmed that CD27 expression distinguished naive and memory cells in SS. In contrast to the peripheral blood, the majority of parotid B cells from 1 patient examined exhibited both the mutational status and phenotype of memory B cells. Accordingly, the mutational frequencies of V_H rearrangements were significantly greater in parotid B cells than in peripheral blood B cells, whereas the V_H gene repertoire appeared to be very similar between the compartments. Conclusion These data indicate that there is an accumulation/retention of memory B cells in the inflamed salivary glands of SS patients. It is possible that preferential accumulation of CD27+ memory B cells in the inflamed parotid gland explains their reduction in the peripheral blood.