Expression of the a, x, and y variable region genes of heavy chains among IgG, IgM, and IgA molecules of normal and a locus allotype suppressed rabbits

The contribution of the V(H) subgroup genes, a, x and y, to the formation of individual IgG molecules has been studied in normal and α locus allotype suppressed rabbits. Using anti x32, anti y33 and antisera to the α locus allotypes (anti a1, anti a2 and anti a3), the authors used indirect precipitation of ¹²⁵I labeled IgG or Fab of specific allotype or inhibition of precipitation for the quantitative analyses. In normal rabbits homozygous with respect to the α locus, about 70 to 90% of the total IgG molecules possess the α locus allotypic specificities and most or all of the remaining molecules, depending on the genotype, could be accounted for as x32 or y33 molecules. Additional IgG molecules with unknown allotypic specificities for the V(H) region were found in two normal a3 rabbits and in an a1 allotype suppressed rabbit; these molecules are probably the products of allelic alternatives to x³² and/or y³³. Allotype suppression of α locus molecules was compensated for by an increase in the number of molecules synthesized by closely linked V(H) subgroup genes, x and y. A similar ratio of the a2, x32, and y33 molecules was observed among Ig fractions with different net electrical charges. In a partially a2 suppressed rabbit, the results of indirect precipitation and sequential precipitation indicated that no two of the allotypic specificities, a2, x32, or y33, are located on the same IgG molecule or on the same Fab fragment. In homozygotes, α locus suppression was found for IgM and IgA as well as for IgG. The expression of a selected V(H) gene in a cell synthesizing Ig molecules results from linked gene exclusion apparently independent of C(H) gene selection.