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  • Title: Chronicity of arthritis induced with homologous type II collagen (CII) in rats is associated with anti-CII B-cell activation.
    Author: Holmdahl R, Vingsbo C, Malmström V, Jansson L, Holmdahl M.
    Journal: J Autoimmun; 1994 Dec; 7(6):739-52. PubMed ID: 7888032.
    Abstract:
    DA rats develop chronic arthritis after immunization with native rat type II collagen (CII) emulsified in incomplete Freund's adjuvant (IFA) (= collagen-induced arthritis, CIA). The same rat strain develops an acute, self-limited form of arthritis after injection with IFA alone (= oil-adjuvant-induced arthritis, OIA). The induction of a chronic course of arthritis, as well as an anti-CII antibody response, was dependent on the dose of CII; 30 micrograms induced a self-limited disease course and no B-cell response, while 150 micrograms induced a chronic disease course and a strong B-cell response. Immunization with denatured rat CII induced only acute arthritis, similar to OIA. To investigate why IFA or denatured CII/IFA induced only acute disease while native CII/IFA induced chronic disease, we analysed the immune responses to CII. Both native and denatured CII induced a weak but significant autoreactive T-cell response while only native CII induced a strong B-cell response to CII. IFA did not produce a significant immune response to CII. Interestingly, rats that had developed acute arthritis after immunization with denatured CII/IFA were vaccinated against CIA, but not rats that had developed arthritis induced with IFA only. Rats vaccinated against CIA after pretreatment with denatured CII/IFA had an anti-CII antibody response that was almost eliminated. In addition, pretreatment of rats with denatured or native rat CII in olive oil, which does not induce arthritis, vaccinated against a subsequent induction of arthritis with native rat CII. Again, the vaccination suppressed the anti-CII B-cell response. We suggest that activated B-cells, reactive with conformational epitopes on CII, are of importance for the chronic development of CIA.
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