Genetic characters of human gamma-globulins in myeloma proteins.

The genetic factors Gm(a), Gm(b), Gm(x), and Inv(a), Inv(b) described for normal human gamma-globulin were all found in different myeloma proteins. A single myeloma protein never contained more than one product of alternate alleles even in heterozygous individuals. However, factors determined by the two different loci were often found in the same myeloma protein. The Gm(a) character of the myeloma protein parallelled that of the normal gamma-globulin of the same serum in most cases. In contrast, the Gm(b) character was usually absent in the myeloma protein when it was directly demonstrable in the normal gamma-globulin. The myeloma proteins from six Negroes were Gm(a+b-), whereas the normal gamma-globulin was Gm(a+b+). This indicates that the effect of gene Gm(b) is similar in Negroes and whites, even though its relation to gene Gm(a) is different in the two races. Gm factors were found only in the 7S gamma-globulin type myelomas and not in other products of plasma cell tumors. Inv characters were, however, present in all four types of proteins studied, namely 7S and 19S gamma-globulins, beta(2A)-globulins, and Bence Jones proteins. In two instances, genetic heterogeneity of the protein products was demonstrated suggesting the proliferation of more than one clone of plasma cells in some multiple myeloma patients. The accumulated evidence obtained in this study strongly suggested that the presence and absence of genetic characters was compatible with the concept that myeloma proteins were closely analogous to individual moieties in the spectrum of normal gamma-globulins rather than truly abnormal proteins. Their study offered evidence of a heterogeneity of genetic characters among the normal gamma-globulins in a given individual. It also appears probable that in normal individuals single plasma cells have a restricted capacity to express genetic information in their protein product.