B Cell Activation, Differentiation, and Their Potential Molecular Mechanisms in Osteoarthritic Synovial Tissue

Abstract

Objective

The objective of this study was to characterize the activation and differentiation of B cells in the synovium of osteoarthritis (OA) and to explore the underlying molecular mechanisms.

Methods

Peripheral blood and synovial samples from OA patients at different stages were collected, and flow cytometry was employed to analyze the activation and differentiation of B cells. Immunofluorescence staining of joint synovium from OA mice at different stages was conducted to assess mice joint synovium B cell activation and differentiation. Co-culture experiments of synovial fibroblasts with B cells were performed to investigate the influence of synovial cells on B cell activation and differentiation. Finally, transcriptome analysis was utilized to identify potential key molecules and pathways.

Results

In OA patients, the infiltration, activation, and differentiation of B cells in synovium and peripheral blood exhibited distinct characteristics. Specifically, the proportion of activated CD86+ B cells and the differentiation marker HLA-DR+ increased with disease severity, whereas the proportion of the differentiation marker IgM decreased. The proportion of CD38+ B cells also decreased with increasing severity, although this change lacked statistical significance. Immunofluorescence staining of CD19+ and CD86+ cells in mice indicated increased expression with greater OA severity. Co-culture experiments demonstrated that OA synovial fibroblasts promoted B cell activation and differentiation, as evidenced by higher expression levels of CD86+ and HLA-DR+ in the OA group compared to controls. Additionally, the proportion of naive B cells decreased as disease severity progressed.

Conclusion

Synovial fibroblasts in OA have been shown to promote the differentiation and activation of B cells, indicating that B cells play a significant role in the pathogenesis of synovium inflammation in OA.