RT Journal Article SR Electronic T1 Synoviocytes-derived Interleukin 35 Potentiates B Cell Response in Patients with Osteoarthritis and Rheumatoid Arthritis JF The Journal of Rheumatology JO J Rheumatol FD The Journal of Rheumatology SP 563 OP 573 DO 10.3899/jrheum.161363 VO 45 IS 4 A1 Ngar-Woon Kam A1 Dehua Liu A1 Zhe Cai A1 Wah-Yan Mak A1 Chun-Kwok Wong A1 Kwok-Hing Chiu A1 Kam-Yiu Wong A1 Wai-Leuk Tsang A1 Lai-Shan Tam YR 2018 UL http://www.jrheum.org/content/45/4/563.abstract 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.