The genetic basis of antibody production: the dominant anti-arsonate idiotype response of the strain A mouse

Abstract

Immunization of the A strain of mice with the hapten p-azophenylarsonate (Ars) results in an immune response in which approximately 50% of the anti-Ars antibodies share cross-reactive idiotypic determinants (IdCR). A gene or genes linked to the heavy chain constant region locus is required for the production of this idiotype. The expressed VH gene from a hybridoma cell line which expresses the IdCR has been cloned. DNA hybridization studies utilizing the VH gene have revealed that there are many related genes in both idiotype-producing and idiotype-nonproducing strains of mice. However, under stringent hybridization conditions, only a single band of 6.4 kb is present in Eco R1-digested A strain DNA. Strains of mice which are phenotypically idiotype-negative either lack this band completely or possess a much weaker one at this position. Utilizing DNA from Igh recombinant strains of mice, it has been shown that the VH locus controlling idiotype expression contains the structural gene information for the idiotype-positive heavy chains. It has also been shown that DNA at this locus appears to be sufficient for the production of the cross-reactive idiotype. Utilizing a DNA probe derived from regions flanking the structural gene has confirmed the relatedness of V genes in a variety of mouse strains and revealed a significant degree of polymorphism at the Igh locus.