BAFF from bone marrow-derived mesenchymal stromal cells of rheumatoid arthritis patients improves their B-cell viability-supporting properties.
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.
2nd Department of Paediatrics, Medical Faculty, Comenius University, Bratislava, Slovak Republic. dallostomas@yahoo.co.uk
T
T
Dallos
M
M
Krivosíková
M
M
Chorazy-Massalska
E
E
Warnawin
E
E
Zánová
W
W
Rudnicka
A
A
Radzikowska
W
W
Maśliński
D000818:Animals; D018951:Antigens, CD20 / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology; D053264:B-Cell Activating Factor / Q000378:metabolism*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D018920:Coculture Techniques; D006801:Humans; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D010003:Osteoarthritis / Q000276:immunology / Q000473:pathology; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism*
D018951:Antigens, CD20; D053264:B-Cell Activating Factor