Antigenic Specificity of Anti-Erythrocyte Autoantibody Responses by NZB Mice: Identification and Partial Characterization of Two Erythrocyte Surface Autoantigens

Abstract

Two independent but coexistent spontaneous anti-erythrocyte autoantibody responses by NZB mice are described. The two specific murine erythrocyte surface antigens uniquely associated with these autoantibody responses, and thus referred to as autoantigens, are identified and partially characterized. Both appear to represent species-specific antigens and are not recognizably segregated on a genetic basis within six strains of mice. One response is directed against an exposed erythrocyte surface determinant herein referred to as the X antigen. This response may be of primary significance in the pathogenesis of the autoimmune hemolytic anemia of NZB mice. The second type of autoantibody response is directed to a site, unexposed on the normal murine erythrocyte surface but exposed by proteolysis with bromelin, and is referred to as the HB antigen. An alternative mechanism for HB antigen exposure and binding of anti-HB autoantibody appears to be mediated by in vivo erythrocyte surface modification, possibly secondary to the binding of anti-X autoantibody in vivo. Specific assays are described for each of these generically independent autoantibodies and erythrocyte surface antigens. The possible implication of these autoantigens in the immune complex disease of the NZB strain is also suggested.