Two types of γG4 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 γG classes. The distinctive antigen of the common 4a type was shared with all γG1 and γG3 proteins but missing in those of the γG2 class; that for the rarer 4b type was selectively found in proteins of the γG2 class.
Analyses on γG4 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 γG 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 γG4 class arose relatively early and preceded the development of those for the other γG classes.