Objective : Collagen-induced arthritis (CIA) is a widely used experimental model of rheumatoid arthritis (RA). As in the case of human RA, mouse CIA is associated with particular haplotypes of H-2, the mouse MHC (major histocompatibility complex). In addition to H-2-linked gene, non-H-2-linked genes also seem to be involved in the pathogenesis of CIA. In this study, we investigated the possible contribution of immunoglobulin heavy chain (Igh) gene allotype to the development of mouse CIA.
Materials and Methods : The B6.Igh
a- congenic strain (H-2
b, Igh
a) was established by introducing Igh
a allotype into C57BL/6 (B6) mice bearin the H-2
b and Ighb allotype. The IgG Fc receptor γ chain (FcR γ) -deficient B6.Igh
a. FcR γ
-/- strain was established by crossing B6.Igha and B6.FcR γ
-/- mice. These mice were immunized with bovine type II collagen, and clinical and histological findings were evaluated to estimate, disease severity.
Results : B6 mice did not develop CIA, because of the CIA-resistant H-2
b haplotype. In contrast, B6.Igh
a- congenic mice developed CIA despite the H-2
b haplotype. The incidence of CIA was significantly higher in male (54.4%) than in female mice (20%) (P<0.05). Serum levels of IgG1 and IgG2a antibodies to type II collagen were up-regulated in B6.Igh
a mice, as compared to those in B6 mice. Interestingly, B6.Igh
a. FcR γ
-/- mice showed anti-collagen antibodylevels comparable to those in B6.Igh
a mice ; however, B6.Igh
a FcRγ
-/- mice did not develop CIA.
Conclusions : Our data suggest that Igh allotype contributes to the development of CIA through the up-regulation of anti-collagen antibody production and that FcR γ -mediated signals via immune complexes composed of anti-collagen antibodies and collagen play an important role in the effector phase of inflammation in CIA.
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