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

Immunogenetics. 1991;34(4):231-41. doi: 10.1007/BF00215258.

Abstract

p-azophenylarsonate-specific antibodies of A/J mice which bear the Ars-A crossreactive idiotype utilize the V kappa-Ars-A gene segment, a member of the V kappa 10 family. Southern hybridization of genomic DNA from several inbred strains using a probe from the 5' flanking region of the V kappa-Ars-A gene demonstrated three patterns of restriction 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: AKR1 (Igk-V10.1a), AJ1 (Igk-V10.1b) and PERU1 (Igk-V10.1c); AKR2 (Igk-V10.2a), AJ2 (Igk-V10.2b), and PERU2 (Igk-V10.2c). The Igk-V10.1b gene of the A/J strain is the V kappa-Ars-A gene used in Ars-A idiotype-positive antibodies. The product of the C.AKR allele (Igk-V10.1a) contained four amino acid substitutions in CDR3 as compared with Igk-V10.1b. These substitutions probably explain the failure of AKR mice and other strains with the same V kappa 10 RFLP pattern to provide in genetic crosses a L chain which, together with the A/J VH-ArsA gene product, form Ars-A idiotype-positive antibodies. Also, the nucleotide sequence identity between the Igk-V10.1c and Igk-V10.1b alleles and the Igk-V10.2c and Igk-V10.2b alleles is significantly greater than that seen in comparisons with the Igk-V10.1a and Igk-V10.2a 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-V10.1b and Igk-V10.2b alleles. Strongly A48 idiotype-positive antibodies utilize the Igk-V10.1b chain, and weakly A48-positive antibodies use the Igk-V10.2b L chain. The possible effects of amino acid substitutions specified by the Igk-V10.1a, Igk-V10.1c, Igk-V10.2a, and Igk-V10.2c alleles on their ability to provide L chains used in A48 idiotype-positive antibodies are discussed.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blotting, Southern
  • Cross Reactions
  • Genes, Immunoglobulin*
  • Immunoglobulin Idiotypes / immunology*
  • Immunoglobulin Variable Region / genetics
  • Immunoglobulin kappa-Chains / genetics*
  • Mice
  • Mice, Inbred A / genetics
  • Mice, Inbred Strains
  • Molecular Sequence Data
  • Polymorphism, Genetic
  • Restriction Mapping
  • Sequence Alignment
  • Sequence Homology, Nucleic Acid
  • p-Azobenzenearsonate / immunology

Substances

  • Immunoglobulin Idiotypes
  • Immunoglobulin Variable Region
  • Immunoglobulin kappa-Chains
  • p-Azobenzenearsonate

Associated data

  • GENBANK/M54903
  • GENBANK/M54904
  • GENBANK/M54905
  • GENBANK/M54906
  • GENBANK/M54907
  • GENBANK/M54908
  • GENBANK/M63950
  • GENBANK/M63951
  • GENBANK/M63952
  • GENBANK/M63953
  • GENBANK/S62777