Polymorphism in V k 10 genes encoding L chains of antibodies bearing the Ars-A and A48 cross-reactive idiotypes

Abstract
P-azophenylarsonate-specific antibodies of A/J mice which bear the Ars-A cross-reactive idiotype utilize the V K−Ars−A gene segment, a member of the V K 10 family. Southern hybridization of genomic DNA from several inbred strains using a probe from the 5′ flanking region of the V K−Ars−A gene demonstrated three patterns of restrictio fragment length polymorphisms (RFLP). Six genes corresponding to hybridizing bands were obtained from DNA libraries of C.AKR, PERU and A/J mice, and nucleotide sequence comparisons revealed two allelic groups: AKRI (Igk-V10.1 a ), AJ1 (Igk-V10.1 b ) and PERU1 (Igk-V10.1 c ); AKR2 (Igk-V10.2 a ), AJ2 (Igk-V10.2 b ), and PERU2 (Igk-V10.2 c ).The Igk-V10.1 b gene of the A/J strain is the V k−Ars−A gene used in Ars-A idiotype-positive antibodies. The product of the C.AKR allele (Igk-V10.1 a ) contained four amino acid substitutions in CDR3 as compared with Igk-V10.1 b . These substitutions probably explain the failure of AKR mice and other strains with the same VK10 RFLP pattern to provide in genetic crosses a L chain which, together with the A/J V H−ArsA gene product, form Ars-A idiotype-positive antibodies. Also, the nucleotide sequence identity between the Igk-V10.1 c and Igk-V10.1 b alleles and the Igk-V10.2 c and Igk-V10.2 b alleles is significantly greater than that seen in comparisons with the Igk-V10.1 a and Igk-V10.2 a alleles, respectively, suggesting an evolutionary pathway similar to that of the linked Igk-J locus. BALB/c antibodies bearing the A48 regulatory idiotype contain L chains encoded by the BALB/c Igk-V10.1 b and Igk-V10.2 b alleles. Strongly A48 idiotype-positive antibodies utilize the Igk-V10.1 b chain, and weakly A48-positive antibodies use the Igk-V10.2 b L chain. The possible effects of amino acid substitutions specified by the Igk-V10.1 a , Igk-V10.1 c , Igk-V10.2 <em...

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