Identification of conformation-dependent epitopes and V gene selection in the B cell response to type II collagen in the DA rat

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Abstract
Collagen-induced arthritis (CIA) is a widely used model for rheumatoid arthritis. Induction of CIA in rats using rat type II collagen (CII) results in a chronic arthritis in which anti-CII antibodies are believed to play a pathogenic role. In this study, we analyzed the epitope selection and V gene usage in the anti-CII response in the DA rat. A panel of CII-reactive B cell hybridomas was established from the draining lymph nodes 11 days after immunization. All of the CII-specific antibodies bound cartilage in vivo, showing that these are true autoantibodies. These antibodies were all IgG and specific for several distinct triple helical epitopes on CII. Interestingly, the major epitope, recognized by four different antibodies, was identical with the major B cell epitope in the mouse CII located at position 359–369 (denoted as C1III). The Q52 and PC7183 VH gene families encoded 12 out of 14 sequenced heavy chains. There was a relatively more heterogeneous usage of VL genes as the antibodies were encoded by four different Vκ families (Vκ1, Vκ2, Vκ12/13 and VκRF). As in the mouse, some of the V genes used showed germline characteristics. We conclude that the immune response in the rat shares epitope specificity and a constrained V gene repertoire with the mouse. However, the V genes used for recognition of the closely related collagen structures differed considerably between mouse and rat, indicating an influence of the species-specific variation in the V gene repertoire.

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