Regulation of synovial B cell survival in rheumatoid arthritis by vascularcell adhesion molecule 1 (CD106) expressed on fibroblast-like synoviocytes

Objective. B lymphocytes accumulate in the inflamed joints of patients with rheumatoid arthritis (RA) and are responsible for production of high amoun ts of (auto)-antibodies, The aim of this study was to determine the capacit y of fibroblast-like synoviocytes (FLS) to contribute to the accumulation o f synovial fluid (SF) B cells by extending their life span. Methods. Highly purified SF B cells were cultured with FLS in the presence or absence of blocking antibodies directed against cell adhesion molecules, and cell viability was determined after various time intervals by trypan b lue, annexin V, propidium iodide, or Hoechst staining. Phenotypic character ization of peripheral blood and SF B cells and FLS was carried out by flow cytometry, Results. Synovial B cells, which consist predominantly of memory B cells an d plasma cells (PC), undergo spontaneous cell death by apoptosis upon remov al from their in vivo environment, despite expression of Bcl-2, Coculture w ith FLS rescued synovial B cells from apoptosis in a cell contact-dependent manner. Blocking studies using monoclonal antibodies demonstrated a role f or the molecular interaction of SF B cells with vascular cell adhesion mole cule 1 (VCAM-1; CD106) in FLS-induced survival. The ability of FLS to induc e SF B cell survival was not related to the rheumatoid origin since FLS fro m non-PA patients had similar properties. Conclusion. These findings indicate a crucial role for FLS in the survival of synovial B cells at the site of inflammation in PA through the interacti on with VCAM-1 expressed on FLS, Consequently, memory B cells and PC accumu lation arise and persist not only as a result of maturation and recruitment of these cells, but also by active prevention from cell death by the micro environment.