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

p-azophenylarsonate-specific antibodies of A/J mice which bear the Ars-A cross-reactive idiotype utilize the V_K–Ars–Agene segment, a member of the V_K10 family. Southern hybridization of genomic DNA from several inbred strains using a probe from the 5 flanking region of the V_K–Ars–Agene 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–Agene 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 V_K10 RFLP pattern to provide in genetic crosses a L chain which, together with the A/J V_H–ArsAgene product, form Ars-A idiotype-positive antibodies. Also, the nucleotide sequence identity between the Igk-V10.1^cand Igk-V10.1^balleles and the Igk-V10.2^cand Igk-V10.2^balleles is significantly greater than that seen in comparisons with the Igk-V10.1^aand Igk-V10.2^aalleles, 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^band Igk-V10.2^balleles. Strongly A48 idiotype-positive antibodies utilize the Igk-V10.1^bchain, and weakly A48-positive antibodies use the Igk-V10.2^bL chain. The possible effects of amino acid substitutions specified by the Igk-V10.1^a, Igk-V10.1^c, Igk-V10.2^a, and Igk-V10.2^calleles on their ability to provide L chains used in A48 idiotype-positive are discussed.The locus name, Igk-V28 (D'Hoostelaere et al. 1988), will be used in this report in place of the name, Igk-VSer, used in the original publications (Goldrick et al. 1985; Boyd et al. 1986; Gottlieb et al. 1986; Ponath et al. 1988). The four alleles described at the Igk-VSer locus (Igk-VSer^a, Igk-VSer^b, Igk-VSer^c, and Igk-VSer^d) are referred to as Igk-V28^a, Igk-V28^b, Igk-V28^c, and Igk-V28^d, respectively.The nucleotide sequence data reported in this paper have been submitted to GenBank nucleotide sequence database and have been assigned the accession numbers M54903, M54904, M54905, M54906, M54907, and M54908.Address correspondence and offprint requests to : P. D. Gottlieb.