Extensive allelic sequence variation in the J region of the human immunoglobulin heavy chain gene locus

Eur J Immunol. 1995 Sep;25(9):2578-82. doi: 10.1002/eji.1830250926.

Abstract

During the initial stages of B lymphocyte differentiation heavy chain variable (VH), diversity (DH) and joining (JH) gene segments recombine to form a functional heavy chain variable region (VDJ) gene. Evidence for genetic polymorphism of the human JH gene segments has been obtained from mature rearranged VDJ sequences. We conducted an analysis of the published rearranged JH gene sequences and found that the JH alleles present in the two published germ-line JH region sequences were rare (approx. 2%) in the rearranged sequences. As an attempt to explain this discrepancy a 2.5-kb strech of DNA containing all the six heavy chain JH region genes and the most 3' DH gene segment, DHQ52, was amplified by the polymerase chain reaction from 39 individuals and analyzed for restriction fragment length polymorphism. Five new JH region haplotypes were found and sequenced. These new haplotypes contained the coding segment alleles that were frequent in antibody genes. Surprisingly, a high number of interallelic differencies in the non-coding sequence was found between the new and the two previously published haplotypes implying that the haplotypes had been separated early in evolution. In this respect the JH locus resembles HLA loci.

MeSH terms

  • Alleles
  • B-Lymphocytes / immunology*
  • Base Sequence
  • Biological Evolution
  • Cloning, Molecular
  • Humans
  • Immunoglobulin Heavy Chains / genetics*
  • Immunoglobulin Heavy Chains / immunology
  • Immunoglobulin J-Chains / genetics*
  • Immunoglobulin J-Chains / immunology
  • Molecular Sequence Data

Substances

  • Immunoglobulin Heavy Chains
  • Immunoglobulin J-Chains

Associated data

  • GENBANK/X86355
  • GENBANK/X86356
  • GENBANK/X86357
  • GENBANK/X86358
  • GENBANK/X86359