The Journal of Experimental Medicine, Vol 132, 508-520,
Copyright © 1970 by The Rockefeller University Press
GENETIC VARIANTS OF 
G4 GLOBULIN
:
A UNIQUE RELATIONSHIP TO OTHER CLASSES OF 
G GLOBULIN
H. G. Kunkel M.D.1,
F. G. Joslin 1,
G. M. Penn M.D.1, and
J. B. Natvig M.D.1
1 From The Rockefeller University, New York 10021, and the Research Institute of Rheumatology, Oslo, Norway
Two types of G4 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 G classes. The distinctive antigen of the common 4a type was shared with all G1 and G3 proteins but missing in those of the G2 class; that for the rarer 4b type was selectively found in proteins of the G2 class.
Analyses on G4 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 G 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 G4 class arose relatively early and preceded the development of those for the other G classes.
Submitted on May 8, 1970
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