Evidence for Control of Synthesis of the Variable Regions of the Heavy Chains of Immunoglobulins G and M by the Same Gene

Previous work indicated that the light chains of a monotypic immunoglobulins G2-K and M-K from a single patient (Ti1) are identical. Our present data show that the monotypic immunoglobulins G and M share idiotypic determinants not present in their isolated light chains or in any of a large number of other immunoglobulins tested, and that amino acid sequences of the first 27 residues from the NH₂-terminal end of the γ- and μ-chains are identical. These results support the hypothesis that at least two genes control the synthesis of each heavy and light chain and suggest that the monotypic immunoglobulin G and monotypic immunoglobulin M of this patient share three of the four genes involved. It is proposed that, during normal immunoglobulin synthesis, different cells of a single clone synthesize immunoglobulins M and G, and that the light chains and the variable segments of the heavy chains of the proteins of the two classes are identical within the clone. A genetic switching mechanism is suggested.