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

Dysregulation of chemokine receptor expression and function by B cells of patients with primary Sjögren's syndrome

“…Recent studies have shown disturbances in peripheral B cell populations in primary SS, with significantly enhanced CD27Ϫ naive and diminished CD27ϩ memory B cells (6,8,9). This was confirmed in the present study.…”

“…The frequency of peripheral CD27ϩ,CD19ϩ memory B cells was significantly reduced in patients with primary SS compared with healthy control subjects (mean Ϯ SD 13.3 Ϯ 12.3% versus 25.6 Ϯ 7.2%; P Յ 0.0014), whereas the frequency of CD19ϩ,CD27Ϫ naive B cells was significantly enhanced in patients with primary SS (mean Ϯ SD 86.1 Ϯ 12.0% versus 74.4 Ϯ 7.2%; P Յ 0.0014) as reported previously (6,8,9). To ensure that these alterations in patients with primary SS did not further influence the analyses, either CD19ϩ,CD27Ϫ or CD19ϩ,CD27ϩ B cells were gated, and the chemokine receptor expression was subsequently analyzed within each subpopulation ( Figures 1A and B).…”

“…In addition, PBMCs were also analyzed, mononuclear cells were prepared, as previously described (6,7), from minor salivary gland biopsy samples from 4 patients with primary SS and 1 female patient with nonspecific sialadenitis.…”

“…The lymphoid infiltrates within the inflamed glands often contain germinal center (GC)-like structures consisting of T and B cell aggregates with proliferating lymphocytes and a network of follicular dendritic cells and activated endothelial cells (3,4). Besides antigen-driven clonal proliferation of B cells (3,5), analyses of inflamed glandular tissue from patients with primary SS also reveal a polyclonal accumulation of CD27ϩ memory B cells and CD27 high plasma cells (6,7). Moreover, immunophenotyping studies indicate that there is disturbed B cell homeostasis in patients with primary SS, with diminished frequencies and absolute numbers of peripheral CD27ϩ memory B cells (6,8,9).…”

“…Besides antigen-driven clonal proliferation of B cells (3,5), analyses of inflamed glandular tissue from patients with primary SS also reveal a polyclonal accumulation of CD27ϩ memory B cells and CD27 high plasma cells (6,7). Moreover, immunophenotyping studies indicate that there is disturbed B cell homeostasis in patients with primary SS, with diminished frequencies and absolute numbers of peripheral CD27ϩ memory B cells (6,8,9). More recently, a single-cell messenger RNA (mRNA) study showed further abnormalities, especially in the mechanisms of heavy chain switch recombination (10).…”