Genetics and primary structure of Vκ gene segments encoding antibody to streptococcal group A carbohydrate. Comparison of Vκ gene structure with idiotope expression

Two gene segments, Vκ-25-39 and Vκ-25-47, that encode antibody to streptococcal group A carbohydrate in A/J mice were found to be more than 95% homologous in nucleotide sequence in both coding and noncoding regions. It was previously shown that Vκ-25-39 encodes immunoglobulins that express the IdX and IdI-1 idiotopes, whereas Vκ-25-47 encodes IdX⁺, and IdI-1^- immunoglobulins. Vκ gene segments that were clearly allelic to Vκ-25-47 are used to encode IdX⁺, IdI-1^- anti-group A carbohydrate antibodies by C.B20 mice and likely by C57BL/6 mice. Murine strains that are deficient in IdI-1 idiotope expression were investigated by Southern blotting with a 5' probe from Vκ-25-39. Two IdI-1-deficient strains, CE/J and C58/J, had a grossly altered Vκ gene segment structure compared with the A/J prototype. In contrast, the IdI-1-deficient strain, C57BL/6, was indistinguishable from A/J with the 5'Vκ-25-39 probe, indicating that more subtle genetic changes account for the loss of IdI-1 expression in C57BL/6 mice. The evolution of Vκ-25-39 and Vκ-25-47 gene segments was deduced by comparison with the homologous Vκ24B gene segment of Mus pahari. Vκ-25-39 and Vκ-25-47 likely have recently duplicated once in A/J and related strains of laboratory mice and may have duplicated again in CE/J mice. Thus, individual members of the Vκ24 gene family, to which Vκ-25-39 and Vκ-25-47 belong, are preserved while the number of gene copies expands or contracts. This fact is strong evidence that evolutionary forces have maintained the Vκ24 gene family, all of which encode antibody specific for carbohydrate found in bacterial pathogens.