Antigen presentation of Type II collagen in rats

Collagen-induced arthritis (CIA) is a T-cell dependent disease of rats whic h follows immunization with bovine type II collagen (bCII). Susceptibility to CIA is linked to the genes encoding the major histocompatibility complex (MHC), suggesting that antigen presentation is important in disease pathog enesis. Antigen-presenting cells (APC) (macrophages, dendritic cells (DC) a nd B cells) were prepared from WA/KIR/KCL rats and presentation of antigen, in the form of native protein (bCII) or synthetic peptide (bCII:184-198), was assessed in T-cell proliferation assays. Whilst macrophages inhibited p roliferative responses to bCII, splenic or thymic low density cells, enrich ed for DC, presented both bCII and bCII(184-198) peptide. However, bone mar row-derived DC, which stimulated T-cell responses to OVA, failed to present bCII, suggesting differences in processing of these two antigens. B-cell d epletion from lymph node cells abrogated the proliferative response to bCII and reconstitution of a T-cell population with B cells restored the prolif erative response, indicating that B cells are important for stimulating T-c ell responses to bCII. B cells play a critical role in CIA by producing pat hogenic anti-bCII antibodies, and we propose that B cells are also importan t APC which present bCII to CD4(+) T cells.