Autoreactivity to collagen in a murine lupus model

Abstract

MRL/l mice exhibit many characteristics of human systemic lupus erythematosus including antinuclear antibodies, circulating immune complexes, glomerulonephritis, and death secondary to renal failure. In addition, these mice have elevated levels of rheumatoid factor and spontaneously develop arthritis that has many similarities to human rheumatoid arthritis. Our present studies indicate that, with age, they also develop reactivity to types I and II collagen. The levels of antibodies against native or denatured types I and II collagen in the sera of 4-5-month-old MRL/l mice are significantly higher than those in the sera of age-matched Balb/c or MRL/n mice. The specificity of these antibodies for collagen was demonstrated by a competitive binding assay. The T cells from 1- or 2-month-old MRL/l mice exhibited a significant proliferative response in the presence of type I collagen and a mild or no response to type II collagen. Both antigenic and mitogenic responses decreased with age. The results suggest that the development of autoimmunity to collagen may play an important role in the perpetuation of arthritis, vasculitis, and glomerulonephritis in MRL/l mice.