Segregation at a locus determining an immunoglobulin genetic marker for the light chain variable region affects inheritance of expression of an idiotype

Abstract

Previous investigations have demonstrated close genetic linkage between loci governing expression of strain-specific idiotypes and immunoglobulin heavy (H) chain allotype (i.e., the CH locus). This linkage is presumed to reflect polymorphism of VH genes (or of their expression) linked to the polymorphic CH locus. That there was no apparent involvement of light (L) chain loci (thought to be unlinked to H chain) in inheritance of the idiotype-positive (Id+) phenotype was surprising, because the L chain is required for formation of each of the idiotypes studied at the chemical level. However, previous studies involving backcrosses of F1(Id+ .times. Id-) mice to the Id- parental strain have never employed as the Id- parent one of several inbred strains shown by Edelman and Gottlieb to express a VL-region polymorphism. Among backcrosses performed in the present study, one involved the A/J strain as the Id+ parent and the PL/J strain, one of the several strains with an L chain polymorphism, as the Id- parent. Whereas in 3 other backcrosses performed, idiotype expression segregated with H chain allotype, in the backcross to PL/J, all mice producing the characteristic A/J Id+ phenotype were A/J allotype+, but not all A/J allotype+ mice were Id+. Typing of backcross progeny for the Ly-3 thymocyte alloantigens, controlled by a locus closely linked to that governing the L chain polymorphism (called the VK-1 locus), indicated that only the Ly-3 heterozygotes expressed the characteristic A/J Id+ phenotype. Thus, all Id+ backcross mice inherited both the H chain allotype and the Ly-3 locus (and closely linked L chain-related locus) from the Id+ A/J strain. When strains with L chain polymorphisms are included in genetic studies of idiotype expression, segregation of loci governing L chain expression may be found to contribute to inheritance of the Id+ character. These studies may also be taken as further evidence that the VL-region repertoire of the PL/J strain may differ considerably from that of most other inbred strains of mice.