Immunobiology of the autoantibody response. I. Circulating analogues of erythrocyte autoantigens and heterogeneity of the autoimmune response of NZB mice.

Anti-erythrocyte autoantibodies of two distinct antigenic specificities can be recovered from immunoglobulin-coated NZB erythrocytes. These autoantibodies react with either exposed (X) or hidden (HB) antigenic determinants on murine red cells and both types can be neutralized by mouse plasma. Antibody neutralization by plasma is dependent on two distinct plasma activities which appear to be soluble analogues of the erythrocyte surface autoantigens X and HB. The soluble erythrocyte antigens SEA-X and SEA-HB can be separated by molecular exclusion chromatography, with approximate sizes of 2 × 10 for SEA–X and ≥ 5 × 10 for SEA-HB. The presence of these soluble erythrocyte autoantigens in the plasmas of `autoimmune' NZB mice has to be considered in relation to the immunologic homeostasis of these autoantibody responses and pathogenesis of both the autoimmune haemolytic anaemia and the autologous immune complex disease of these mice. Individual anti-erythrocyte autoantibodies of both anti-X and anti-HB types exhibit discrete and individually distinctive differences in affinity for autoantigen and also in respect to antigenic determinant specificity. These results suggest that factors which control the genetic selection of these responses in an inbred strain do not prescribe a single specific B lymphoid cell clone; but rather it appears that a number of different autoimmunocompetent B lymphocyte clones with differing affinity and determinant specificity for given autoantigen molecules may be dere-pressed by other events in the recruitment of the autoantibody responses.