Background Rheumatoid arthritis (RA) is a common and complex autoimmune disease characterized by chronic inflammation and cartilage/bone damage involving numerous cells, such as T cells, B cells, chondrocytes, fibroblasts . B cells had long been well-demonstrated to participant in the development of RA . Except producing specific antibody and inducing T cell activation, impaired immunosuppressive function of B cells further emphasized their roles in RA recently .
Objectives To investigate whether B cells could produce granzyme B and the potential role in the pathogenesis of Rheumatoid arthritis (RA).
Methods To reveal the expression of granzyme B in B cells, flow cytometry, PCR and Elispot were performed. The role of IL-21 and anti-BCR stimulation on granzyme B expression was assessed by in vitro stimulation assay. CD4+ T cell-B cell co-culture in the presence of granzyme B neutralizing antibody was performed to demonstrate the function of these cells. Then the levels of granzyme B in B cells between RA patients, OA patients as well as HCs were compared. Next,the correlation analysis between granzyme B-producing B cells and clinical features in RA patients was performed. Finally, the frequencies of granzyme B-producing B cells in RA patients before and after therapy were also evaluated using flow cytometry.
Results B cells could spontaneously produce granzyme B, which could be perpetuated by IL-21 and anti-BCR stimulation. The frequencies of Th1 and Th17 cells were significantly elevated under the condition of granzyme B blockade when granzyme B was neutralized in CD4+ T cell-B cell co-culture. In RA patients, but not OA patients and HCs, the frequencies of granzyme-B producing Bregs decreased significantly, which was functionally impaired and negatively correlated with disease activity score 28. Moreover, after effective clinical therapy, the frequencies could recover to nomal levels.
Conclusions B cells could exert the regulatory functions via granzyme B production. Under RA circumstance, these granzyme B-producing Bregs were impaired and contributed to the disease progression.
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Acknowledgements This study was supported by grants from the Natural Science Foundation of China (81671609, 81671604,31470039).
Disclosure of Interest None declared
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