In this study, based on the key finding that RANKL was expressed at high levels in CD80+CD86+ B cells from patients with RA, we demonstrate that, upon activation via B-cell receptor (BCR) and CD40, human switched-memory B cells predominantly expressed RANKL, which was further augmented by interferon (IFN)-γ but suppressed by interleukin (IL)-21. Here, IFNG is linked to rheumatoid arthritis.