Chronicity of arthritis induced with homologous type II collagen (CII) in rats is associated with anti-CII B-cell activation.
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.
Holmdahl
R
R
Department of Medical Inflammation Research, Lund University, Sweden.
Vingsbo
C
C
Malmström
V
V
Jansson
L
L
Holmdahl
M
M
D000818:Animals; D000961:Antilymphocyte Serum; D001168:Arthritis / Q000276:immunology*; D001169:Arthritis, Experimental / Q000276:immunology; D001323:Autoantibodies / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000276:immunology*; D002908:Chronic Disease; D003094:Collagen / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005620:Freund's Adjuvant / Q000276:immunology; D008213:Lymphocyte Activation; D011489:Protein Denaturation; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination
D000961:Antilymphocyte Serum; D001323:Autoantibodies; D003094:Collagen; D005620:Freund's Adjuvant