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Influence of coding-end sequence on coding-end processing in V(D)J recombination

Academic Article
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Overview

authors

  • Nadel, B.
  • Feeney, Ann

publication date

  • November 1995

journal

  • Journal of Immunology  Journal

abstract

  • The large diversity of the Ig and TCR repertoires is accounted for by combinatorial assembly of the germ-line-encoded V, D, and J gene segments, as well as extensive modification at the junctions during the recombination process. Those modifications, termed coding-end processing, consist of removal and addition of an apparently random number of nucleotides. To obtain further insights into the mechanism of the coding-end processing, we constructed a large data base of several Ig and TCR coding ends obtained in vivo, using conditions that avoid potential bias by cellular selection events. We show that the processing patterns are not random, but rather specific for each coding end, suggesting that specific motifs in the coding-end sequence influence the processing. We found a good correlation between the presence of internal stretches of at least three A.T nucleotides, absence of stretches of G.C nucleotides, and high average nucleotide deletion. Based on a detailed analysis of the processing patterns, we propose that nicks of the hairpin intermediate take place preferentially in potential open structures formed by weaker pairings of A.T stretches. Together, these findings indicate that the sequence of the coding end plays an important role in nonrandom aspects of the recombination mechanism. This suggests that coding-end sequences might have been selected throughout evolution to participate in an early control of the development of the primary repertoire.

subject areas

  • Animals
  • B-Lymphocytes
  • Base Sequence
  • Cell Differentiation
  • Codon
  • Gene Library
  • Gene Rearrangement, B-Lymphocyte
  • Genes, Immunoglobulin
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Joining Region
  • Immunoglobulin Variable Region
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Receptors, Antigen, B-Cell
  • Receptors, Antigen, T-Cell
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Identity

International Standard Serial Number (ISSN)

  • 0022-1767

PubMed ID

  • 7594591
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Additional Document Info

start page

  • 4322

end page

  • 4329

volume

  • 155

issue

  • 9

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