Anti-glucose-6-phosphate isomerase (GPI) antibodies from K/BxN mice directly induce arthritis; however, the transfer of these antibodies from mice with GPI-induced arthritis does not induce arthritis. CD4+ T cells play an important role in the induction and effector phase in this model; however, the roles of B cells and immunoglobulins (Igs) have not been elucidated. We investigated the roles of B cells and Igs in GPI-induced arthritis by using adoptive transfer system into SCID mice. Transfer of splenocytes of male DBA/1 mice immunized with GPI into SCID mice induced arthritis on day 6 in the latter, in association with the production of anti-GPI antibodies. Co-localization of C3 and IgG on the articular surface was identified in arthritic SCID mice. Inoculation of IgG (or anti-GPI antibodies) and CD19+-depleted splenocytes from arthritic DBA/1 mice induced arthritis in SCID mice, but not CD19+-depleted or CD4+-depleted splenocytes from DBA/1 mice. In vitro analysis of cytokine production by splenocytes from DBA/1 arthritic mice demonstrated production of large amounts of tumour necrosis factor (TNF)-α and interleukin (IL)-6 in an antigen-specific manner (P < 0·01), and production was dominated by CD19+-depleted than CD4+-depleted splenocytes (P < 0·05). Addition of IgG from DBA/1 arthritic mice to the culture enhanced TNF-α but not IL-6 production, and this effect was blocked by anti-Fcγ receptor antibody. In vivo analysis of neutralization with TNF-α protected arthritis completely in SCID mice. Our results highlight the important role of B cells in GPI-induced arthritis as autoantibody producers, and these autoantibodies can trigger joint inflammation in orchestration with inflammatory cytokines, especially TNF-α
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