Ik. Campbell et al., Collagen-induced arthritis in C57BL/6 (H-2(b)) mice: new insights into an important disease model of rheumatoid arthritis, EUR J IMMUN, 30(6), 2000, pp. 1568-1575
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.