A comprehensive investigation on the distribution of circulating follicular T helper cells and B cell subsets in primary Sjögren’s syndrome and systemic lupus erythematosus

Abstract

SummaryFollicular T helper (Tfh) cells have a crucial role in regulating immune responses within secondary lymphoid follicles by directing B cell differentiation towards memory B cells and plasma cells. Because abnormal humoral responses are key features in both primary Sj€ ogren's syndrome (pSS) and systemic lupus erythematosus (SLE), the aim of this study was to profile the pathological connection between peripheral Tfh cells and B cells in the two diseases. Twenty-five pSS patients, 25 SLE patients and 21 healthy controls were enrolled into the study. We determined the ratio of circulating Tfh-like cells, their interleukin (IL)-21 production and different B cell subsets by flow cytometry. We observed higher percentages of naive B cells in both diseases, while non-switched and switched memory B cells showed decreased frequencies. The proportions of double-negative B cells and plasmablasts were elevated in SLE and decreased in pSS. The percentages of transitional B cells and mature-naive B cells were higher in SLE. Patients with more severe disease course had an elevated ratio of T FHlike cells and increased IL-21 production. Moreover, expansion of Tfh-like cells correlated positively with parameters related to antibody secretion, including serum immunoglobulin (Ig)G, immune complexes (ICs) and autoantibodies. Correlation analysis between Tfh-like cells and certain B cell subsets revealed possible defects during B cell selection. In conclusion, our observations on the profound expansion of circulating Tfh-like cells and their IL-21 production, along with the characteristic aberrant peripheral B cell distribution in both pSS and SLE, indicate the prominent role of Tfh cell in the regulation of B cell selection.

MicroRNA expression profiles identify disease-specific alterations in systemic lupus erythematosus and primary Sjögren's syndrome

“…For the identification of different lymphocyte subpopulations, PBMCs were stained then assessed using flow cytometer, as described previously [17]. For identification of B cell subsets, we used the combination of IgD-fluorescein isothiocyanate (FITC)/CD27-phycoerythrin (PE)/CD19-phycoerythrin-Cyanine dye 5 (PE-Cy5) (Beckman Coulter Inc, Fullerton, CA, USA and Immunotech, Marseille, France) and CD38-FITC/CD27-PE/CD19-PE-Cy5/CD24-allophycocyanin (APC) (BD Biosciences, San Diego, CA, USA and Beckmann Coulter and BioLegend, San Diego, CA, USA).…”

Multiple Roles for B-Lymphocytes in Sjogren’s Syndrome

“…Studies evaluating the subpopulations of B cells in the peripheral blood of patients with SS have measured decreased numbers of CD27+ memory B cells [11,12,13,14]. Genetic evaluation of these cells has identified increased numbers of mutated Ig transcripts, suggesting a high percentage of the CD27+ cells are IgM memory B cells [12].…”

Follicular Helper T Cells in Autoimmunity

“…The role of TFH cells in human SLE, in which autoantibodies are considered as primarily markers of the disease, is yet not well studied. However, it was shown that elevated frequencies of peripheral blood CD4 + CXCR5 + precursor TFH cells were accompanied by increased IL-21 levels and excessive pathogenic autoantibody production in patients with SLE [85]. Equal pathological patterns were observed in other autoimmune diseases such as juvenile dermatomyositis and Sjögren's syndrome [85].…”

“…However, it was shown that elevated frequencies of peripheral blood CD4 + CXCR5 + precursor TFH cells were accompanied by increased IL-21 levels and excessive pathogenic autoantibody production in patients with SLE [85]. Equal pathological patterns were observed in other autoimmune diseases such as juvenile dermatomyositis and Sjögren's syndrome [85]. Increased levels of memory TFH cells and plasma IL-21 were observed in patients with MS compared to healthy controls and patients with complete remission of the disease [86].…”