Antibodies against v-Globulin after Repeated Blood Trans- fusions in Man *

Agglutinators specific for genetically controlled antigenic determinants of human y-globulin are found in serum from patients with rheumatoid arthritis and less frequently in serum from clinically normal donors (1-3). Such agglutinators have been used to define a number of genetic determinants that occur as the Inv factors on the L polypeptide chain and the Gm factors on the H polypeptide chain of human y-globulin (4-6). Recently a high incidence of Gm-specific agglutinators has been found in children who have received repeated blood transfusions (7, 8). This suggested that genetically foreign isologous y-globulin was antigenic in man. Subsequent studies have indicated that placentally transferred, genetically foreign y-globulin from the mother can immunize the human fetus (9-11). Antigenicity of isologous y-globulin in a variety of other animal species has been well established since studies by L'Oudin delineated the genetically controlled allotypes of rabbit y-globulin (12). More recently, a number of workers have shown that autologous y-globulin may be made antigenic in the rabbit by a variety of physical or chemical alterations of the y-globulin molecules (13-15). The development of anti-y-globulin antibodies after immunization of animals (13, 16) and man (17) with a variety of nonglobulin antigens has been demonstrated, presumably due to antigenicity of antigenantibody complexes. The frequent occurrence of anti-Gm agglutinators in serum from patients with rheumatoid arthritis (18) has suggested a close relationship between Gm-specific and other anti-y-globulin activity in these sera. The studies that form the basis of this report were designed to explore the