Essential role of Fc gamma receptors in anti-type II collagen antibody-induced arthritis.

Anti-type II collagen (anti-CII) Ab is a well-known autoantibody observed in patients with rheumatoid arthritis. Injection of anti-CII Ab and LPS induces arthritis in mice in which anti-CII Ab as well as inflammatory cytokines, IL-1beta and TNF-alpha, play critical roles. We investigated the involvement of IgG FcRs (FcgammaRs) in this arthritis model. BALB/c mice injected with the F(ab')(2) of anti-CII Ab showed no signs of arthritis. Arthritis development was not observed in FcRgamma(-/-) mice and was partially suppressed in FcgammaRIII(-/-) mice despite the binding of anti-CII Ab and C3 to cartilage surface. Surprisingly, BALB/c mice lacking FcgammaRIIB, which is known as an inhibitory FcgammaR, developed arthritis with no exacerbation in arthritis score compared with wild-type (WT) mice, and only slight exacerbation was observed in the histopathological analysis. In contrast, aged FcgammaRIIB(-/-) BALB/c mice developed arthritis without LPS injection, suggesting an augmented susceptibility to arthritis in aged FcgammaRIIB(-/-) mice. No significant difference was observed among BALB/c-WT, -FcRgamma(-/-), and -FcgammaRIIB(-/-) mice on cytokine production induced by anti-CII Ab and LPS injection. Severe arthritis developed in BALB/c-WT and -FcgammaRIIB(-/-) mice, but not in BALB/c-FcRgamma(-/-) mice, after the injection of anti-CII Ab and inflammatory cytokines. These results suggest that the reason behind the nondevelopment of arthritis in FcRgamma(-/-) BALB/c mice is not due to a disorder in transient cytokine production, but to an irregularity downstream of cytokine production.