IgM+CD27+ B cells possessed regulatory function and represented the main source of B cell-derived IL-10 in the synovial fluid of osteoarthritis patients

Abstract

Synovial inflammation is observed in patients with osteoathritis (OA) and likely contributed to its exacerbation. Regulatory B (Breg) cells are shown to suppress inflammation in various diseases, including rheumatoid arthritis (RA). To examine whether Breg cells also participated in OA, we examined the synovial fluid from OA patients, and compared with that in RA patients. In OA synovial fluid, IL-10-producing B cells were present directly ex vivo and were increased upon stimulation, indicating that B cells were a source of IL-10 directly at the affected site of OA patients. Interestingly, the frequency of IL-10⁺ cells in synovial B cells was higher in OA patients than in RA patients, but the total number of IL-10⁺ B cells in OA was lower than that in RA, suggesting that OA patients presented lower B cell infiltration than RA patients. Phenotypical analysis demonstrated that the IL-10⁺ B cells were IgM⁺ and CD27⁺, but not CD24^hi or CD38^hi. To allow functional analysis of IgM⁺CD27⁺ B cells, the IgM⁺CD27⁺ B cells in the blood of OA patients were examined. These blood IgM⁺CD27⁺ B cells expressed more IL-10, but less CD80 and CD86 than non-IgM⁺CD27⁺ B cells. Blood IgM⁺CD27⁺ B cells suppressed the proliferation and IFN-γ expression of autologous T cells, and this effect could be reverted if IL-10 was inhibited. Furthermore, we found that patients with more severe OA presented lower levels of IL-10⁺ B cells in the synovial fluid. Together, our study described an IgM⁺CD27⁺ B cell subset in OA patients, which represented the major IL-10-secreting B cell type in the synovial fluid of OA patients and possessed regulatory function.

Keywords: Breg; IL-10; Osteoarthritis.