Genetic variants of G4 globulin. A unique relationship to other classes of G globulin.

Two types of gammaG4 proteins, termed 4a and 4b, were characterized through antigenic studies of myeloma proteins. Both were recognized by specific antigens on the Fc fragment which were shared with other gammaG classes. The distinctive antigen of the common 4a type was shared with all gammaG1 and gammaG3 proteins but missing in those of the gammaG2 class; that for the rarer 4b type was selectively found in proteins of the gammaG2 class. Analyses on gammaG4 fractions isolated from normal sera showed that either the 4a or the 4b or a mixture of the two types was present in each serum. Evidence was obtained that these differences were on a genetic basis and that allelic genes linked to those of the Gm system were involved. Such a reciprocal occurrence in other classes of gammaG globulin of the antigenic markers distinguishing genetic variants has not been observed previously. A number of questions regarding the evolutionary development of the genes responsible are discussed. The possibility is raised that those for the gammaG4 class arose relatively early and preceded the development of those for the other gammaG classes.