PT - JOURNAL ARTICLE AU - Ngar-Woon Kam AU - Dehua Liu AU - Zhe Cai AU - Wah-Yan Mak AU - Chun-Kwok Wong AU - Kwok-Hing Chiu AU - Kam-Yiu Wong AU - Wai-Leuk Tsang AU - Lai-Shan Tam TI - Synoviocytes-derived Interleukin 35 Potentiates B Cell Response in Patients with Osteoarthritis and Rheumatoid Arthritis AID - 10.3899/jrheum.161363 DP - 2018 Apr 01 TA - The Journal of Rheumatology PG - 563--573 VI - 45 IP - 4 4099 - http://www.jrheum.org/content/45/4/563.short 4100 - http://www.jrheum.org/content/45/4/563.full SO - J Rheumatol2018 Apr 01; 45 AB - Objective. Elevated expression of interleukin 35 (IL-35) is associated with autoimmune disease, including rheumatoid arthritis (RA). The present study was undertaken to determine the functional interaction among IL-35, B cells, and stromal cells residing in the synovium of patients with RA and osteoarthritis (OA).Methods. IL-35 (EBI-3/p35) expression was investigated in RA and OA synovium using quantitative real-time PCR (qRT-PCR) and immunohistochemistry. IL-35 receptor (IL-35R) expression on B cells dissociated from synovium and periphery of patients with RA, OA, and healthy donor controls (HC) was determined by flow cytometry. The degree of B cells activation after IL-4 and/or IL-35 stimulation was measured by flow cytometry and qRT-PCR. Synovial fibroblasts (SF) purified from RA and OA synovium were cocultured with peripheral HC B cells in the presence/absence of tumor necrosis factor-α (TNF-α) and with/without anti-IL-35–blocking antibodies.Results. EBI-3/p35 transcripts were expressed in close proximity to B cells residing in RA and OA synovium. IL-35R subunits, gp130 and IL-27Rα, but not IL-12Rβ2, were expressed in B cells extracted from the synovium and periphery of patients with RA/OA. Notably, RA synovium expressed the highest level of IL-27Rα on their cell surface. IL-35 induced proliferation and IgG production in HC B cells. Cocultures of HC B cells with RASF, but not OASF, exhibited significantly elevated B cells activation. TNF-α–induced, RASF-dependent secretion of IgG in B cells is partly IL-35–dependent.Conclusion. To our knowledge, for the first time we demonstrated that synovial/peripheral B cells expressed IL-35R and were responsive to IL-35 stimulation. SF residing in RA synovium can be linked to B cell activation and maintenance in RA synovium through IL-35.