Evidence for multiple gene control of a single polypeptide chain: the heavy chain of rabbit immunoglobulin.

To determine the chemical basis for rabbit heavy chain allotypes, amino acid analyses were carried out on IgG and IgM antibodies isolated from rabbits which were homozygous a1 or a3 for the gamma chain locus and homozygous b4 for the light chain locus. The compositional differences between a1 and a3 IgM antibodies were found to be identical to those between their IgG counterparts. The identity of the allotypic amino acid replacements showed that the same genetic markers were present in the variable sequences of IgG and IgM heavy chains. Since the constant sequences of these heavy chains are controlled by different loci, these data demonstrated that rabbit heavy chains are coded by two separate germ-line genes, one producing the variable region and a second one of various genes producing the constant regions. The use of two antibodies, antiazophenylarsonate and antiazophenyl-beta-lactoside, permitted the compositions to be compared also on the basic of immunological specificity. The specificity amino acid replacements were found to be identical in the IgM and IgG heavy chains whether the two antibodies were isolated from and individual animal of a1 or a3 allotype. These results further support the conclusions of the allotype measurements that at least two genes code for the rabbit heavy chain.