Resistance to Development of Collagen-Induced Arthritis in C57BL/6 Mice Is Due to a Defect in Secondary, but Not in Primary, Immune Response

Collagen-induced arthritis (CIA) is a rodent model of human rheumatoid arthritis. Mice of the H-2(q) (DBA/1J) background are highly susceptible to disease whereas mice of the H-2(b) (C57BL/6, B6) background are resistant. To determine why B6 mice are resistant to disease induction, we systematically analyzed T and B cell immune responses in B6 mice, compared to DBA/1J mice, following immunization with bovine type II collagen (CII). We found that both strains showed similar T cell proliferation and cytokine responses and similar levels of anti-CII antibodies (Abs) at day 12 or day 14 of initial immunization (primary immune response), however, those B6 mice that did not develop arthritis showed a significant defect in T cell responses and significantly lower levels of anti-CII Abs following secondary boosting immunization (day 35 of initial immunization, secondary immune response) compared to DBA/1J mice. Our results define for the first time that a defective secondary immune responses in B6 mice leads to the resistance of CIA.