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A defective V-kappa A2 allele in navajos which play play a role in increased susceptibility to haemophilus influenzae type disease

Academic Article
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Overview

authors

  • Feeney, Ann
  • Atkinson, M. J.
  • Cowan, M. J.
  • Escuro, G.
  • Lugo, G.

publication date

  • May 1996

journal

  • Journal of Clinical Investigation  Journal

abstract

  • The antibody response to H. influenzae type b (Hib) is pauciclonal, and is dominated by antibodies using the VkappaA2 gene. Navajos have a 5-10-fold increased incidence of Hib disease compared with control populations. We hypothesized that a polymorphism in one of the genes in this oligoclonal response may lead to increased disease susceptibility. Since the predominant A2+ anti-Hib antibodies have high avidity for Hib and can be unmutated, the A2 Vkappa gene was analyzed. Over half of the Navajos studied, but only one control individual, had a new allele of A2, termed A2b, with three changes from the published A2 germline sequence. One of the changes was in the recombination signal sequence, suggesting that the A2b allele might not undergo V-J rearrangement very frequently. This possibility was confirmed by analyzing the relative frequency of non-productive A2 rearrangements in A2a/b heterozygous Navajos. Many fewer A2b rearrangements were observed, showing that the A2b allele is defective in its ability to undergo rearrangement. The prevalence of this allele in Navajos may play a role in their increased susceptibility to invasive Hib disease. If so, it would underscore the importance of the germline Ig repertoire for protective antibody responses to pathogenic bacteria in unimmunized children.

subject areas

  • Alleles
  • Amino Acid Sequence
  • Antibodies, Bacterial
  • Base Sequence
  • Gene Rearrangement
  • Genes, Immunoglobulin
  • Haemophilus Infections
  • Haemophilus influenzae
  • Humans
  • Immunoglobulin Variable Region
  • Immunoglobulin kappa-Chains
  • Inuits
  • Molecular Sequence Data
  • Promoter Regions, Genetic
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Research

keywords

  • B-lymphocytes
  • antibody diversity
  • gene rearrangement
  • immunoglobulin genes
  • immunoglobulin variable region
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Identity

International Standard Serial Number (ISSN)

  • 0021-9738

Digital Object Identifier (DOI)

  • 10.1172/jci118669

PubMed ID

  • 8636407
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Additional Document Info

start page

  • 2277

end page

  • 2282

volume

  • 97

issue

  • 10

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