B-cell capacity for expansion and differentiation into plasma cells are altered in osteoarthritis |
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| Institution: | 2. Translational Research in Immune Mediated Inflammatory Disease, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK;3. Division of Haematology and Immunology, Leeds Institute of Medical Research, University of Leeds, Leeds, UK;4. Leeds Institute of Health Sciences, School of Medicine, University of Leeds, Leeds, UK |
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| Abstract: | ObjectiveAutoantibody (autoAbs) production in osteoarthritis (OA), coupled with evidence of disturbed B-cell homoeostasis, suggest a potential role for B-cells in OA. B-cells can differentiate with T-cell help (T-dep) or using alternative Toll like recptor (TLR) co-stimulation (TLR-dep). We analysed the capacity for differentiation of B-cells in OA versus age-matched healthy controls (HCs) and compared the capacity of OA synovitis-derived stromal cells to provide support for plasma cell (PC) maturation.MethodsB-cells were isolated from OA and HC. Standardised in vitro models of B-cell differentiation were used comparing T-dep (CD40 (cluster of differentiation-40/BCR (B-cell receptor)-ligation) versus TLR-dep (TLR7/BCR-activation). Differentiation marker expression was analysed by flow-cytometry; antibody secretion (immunnoglobulins IgM/IgA/IgG) by ELISA (enzyme-linked immunosorbent assay), gene expression by qPCR (quantitative polymerase chain reaction).ResultsCompared to HC, circulating OA B-cells showed an overall more mature phenotype. The gene expression profile of synovial OA B-cells resembled that of PCs. Circulating B-cells differentiated under both TLR-dep and T-dep, however OA B-cells executed differentiation faster in terms of change in surface marker and secreted more antibody at Day 6, while resulting in similar PC numbers at Day 13, with an altered phenotype at Day 13 in OA. The main difference was reduced early B-cells expansion in OA (notably in TLR-dep) and reduced cell death. Stromal cells support from OA-synovitis allowed better PC survival compared to bone marrow, with an additional population of cells and higher Ig-secretion.ConclusionOur findings suggest that OA B-cells present an altered capacity for proliferation and differentiation while remaining able to produce antibodies, notably in synovium. These findings may partly contribute to autoAbs development as recently observed in OA synovial fluids. |
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| Keywords: | Osteoarthritis B-cell differentiation Synovial niche |
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