Collagen-induced arthritis in C57BL/6 (H-2(b)) mice: new insights into an important disease model of rheumatoid arthritis

Collagen-induced arthritis (CIA) is a widely used model of rheumatoid arthr itis (RA) and has been important for understanding autoimmunity. CIA is pur portedly restricted to mice bearing the MHC class II H-2(q) or H-2(r) haplo types. In this study, we re-examined established concepts regarding suscept ibility to CIA. We found mice derived from the C57BL/6 (B6) (H-2(b)) backgr ound can develop CIA with high incidence (60-70%), and sustained severity b y using an immunization procedure modified for optimum response in DBA/1 (D 1) (H-2(q)) mice. Clinically and histologically the B6 disease resembles th at of D1 mice and is dependent on immunization with type II collagen, as we ll as on B and CD4(+) T cells. In contrast, 129/Sv mice, which share H-2(b) , are resistant to CIA. We conclude that susceptibility to CIA may reflect immunization conditions and/or important contributions from non-MHC genes, revealed by different immunization protocols. A practical outcome is that C IA can be directly applied to gene knockout mice generated from B6 embryoni c stem cells without need for backcross onto the D1 background. This model may lead to improved understanding of autoimmunity in CIA and RA and may pr ovide a platform for analysis of the contribution of non-MHC genes to CIA.