Expression of FcgammaRIII is required for development of collagen-induced arthritis.
Circulating immune complexes are implicated in the pathogenesis of rheumatic immune disorders and the interaction of these immune complexes with IgG Fc receptors (FcgammaR) seems to be a determining step in the initiation of the inflammatory process. Mice deficient in the FcRgamma-chain, and thus lacking multiple FcR, have previously been shown to be protected from collagen-induced arthritis (CIA). However, the relative contribution of the different FcgammaR has not been identified. In this study, we investigated the expression and contribution of FcgammaRIII, the activating low-affinity FcgammaR in the development of CIA. Wild-type and FcgammaRIII-deficient DBA/1 (FcgammaRIII(-/-)) mice were immunized with bovine collagen type II (BCII) in Freund's complete adjuvant and arthritis development was evaluated by clinical and histological examinations. We found that FcgammaRIII(-/-) mice developed virtually no arthritis in contrast to wild-type mice, the majority of which developed severe CIA. Although resistant to CIA, the humoral and cellular responses to BCII in FcgammaRIII(-/-) mice were similar to that seen in wild-type controls. FcgammaRIII expression was studied on sections from normal joints of FcgammaRII-deficient DBA/1 mice stained with the mAb 2.4G2, specific for FcgammaRII and FcgammaRIII. FcgammaRIII was demonstrated in cells of the lining and sublining layer of the synovial membrane. We conclude that development of CIA requires FcgammaRIII and that expression of FcgammaRIII on synovial cells may contribute to the antibody-triggered inflammation in joints.
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000209:etiology* / Q000473:pathology; D024043:Collagen Type II / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000145:classification; D008213:Lymphocyte Activation; D051379:Mice; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D017452:Receptors, IgG / Q000032:analysis / Q000502:physiology*; D013583:Synovial Membrane / Q000276:immunology
D024043:Collagen Type II; D007074:Immunoglobulin G; D017452:Receptors, IgG