Naturally occurring autologous anti-idiotypic antibodies. Participation in immune complex formation in selective IgA deficiency

50% of individuals with selective IgA deficiency have high serum titers of antibody to bovine proteins, and high levels of circulating immune complexes that contain bovine antigens. Because in animal studies, immunization with antigen-antibody complexes is a very effective means of producing anti-idiotypic antibodies, we sought such autoantibodies in two sera known to have large amounts of anticasein. After IgG isolation and two-stage affinity chromatography, IgG-like material (molecular weights of H and L chains on SDS-PAGE), with binding activity for the F(ab')₂ of anticasein were isolated from both sera. Pooled human gamma globulin or IgG myeloma protein did not inhibit binding of specific anti-anticaseins to the corresponding anticasein, but sodium caseinate did block this binding (by 80 and 95%) indicating that most of these autoantibodies have affinity for the casein-binding site. Naturally occurring anti-idiotypic antibodies have been difficult to conclusively demonstrate in human sera; consequently, these experiments provide evidence of a unique model which may be used to explore the network theory of immunoglobulin regulation in humans.