BAFF from bone marrow-derived mesenchymal stromal cells of rheumatoid arthritis patients improves their B-cell viability-supporting properties.

Abbreviations: Ab – antibody, APC – antigen-presenting cell, ARA – American Rheumatism Association, BAFF – B cell-activating factor, BCMA – B-cell maturation antigen, BM – bone marrow, CIA – collagen-induced arthritis, FLS – fibroblast-like synoviocyte, FSC – forward-scatter, GC – germinal centre, Ig – immunoglobulin, mAb – monoclonal antibody, MRI – magnetic resonance imaging, MSC – mesenchymal stromal cell, PBMC – peripheral blood mononuclear cell, OA – osteoarthritis, RA – rheumatoid arthritis, RF – rheumatoid factor, SLE – systemic lupus erythematosus, SSC – side-scatter, TACI – transmembrane activator calcium modulator cyclophillin ligand interactor. Abstract. Mesenchymal stromal cells (MSCs) represent a unique cell type with anti-proliferative effects on activated T and B cells. Based on our observation of differences between rheumatoid arthritis and osteoarthritis bone marrow B cells we hypothesized that rheumatoid arthritis bone marrow MSCs may enhance B-cell survival. We aimed to compare the effect of rheumatoid arthritis and osteoarthritis bone marrow-derived MSCs (rheumatoid arthritis MSCs, osteoarthritis MSCs) on the survival of healthy donor purified B cells. Rheumatoid arthritis and osteoarthritis MSCs were isolated from patients undergoing hip replacement surgery, and cultured in vitro for 2–5 passages. Washed cells were co-cultured with CD20 B cells for 30–90 hours. Cell survival was analysed using 7-amino-actinomycin D labelling by flow cytometry. Expression of mRNA and protein was determined by RT-PCR and flow cytomery. Co-culture with both rheumatoid arthritis MSCs and osteoarthritis MSCs significantly enhanced B-cell survival, the effect being more prominent in rheumatoid arthritis MSCs. Both types of MSCs displayed expression of B cell-activating factor mRNA and protein. Blocking B cell-activating factor signalling from MSCs by specific anti-B cell-activating factor and anti-B cell-activating factor receptor antibodies weakly reversed the effect of MSCs on B-cell survival mainly in rheumatoid arthritis MSCs. MSC interaction with B cells provides stimuli for B-cell survival and therefore may contribute to the pathogenesis of rheumatoid arthritis. MSC-derived factors other than B cell-activating factor are likely to contribute to this effect. This feature is more prominent in rheumatoid arthritis MSCs, possibly due to the B cell-activating factor.