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Beyond the 12/23 rule of VDJ recombination independent of the Rag proteins

Academic Article
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Overview

authors

  • Olaru, A.
  • Petrie, Howard
  • Livak, F.

publication date

  • May 2005

journal

  • Journal of Immunology  Journal

abstract

  • The combinatorial repertoire of AgRs is established through somatic recombination of V, D, and J gene segments during lymphocyte development. Incorporation of D segments into IgH, TCRbeta, and TCRdelta chains also contributes to junctional diversification by substantially extending the length of the third CDR. The V, D, and J gene segments are flanked by recombination signals (RS) of 12- or 23-mer spacer length that direct recombination according to the 12/23 rule. D genes in the TCRbeta and TCRdelta loci are flanked by a 12RS and 23RS, and their incorporation is controlled by mechanisms "beyond the 12/23 rule." In the TCRbeta locus, selective interactions between Rag proteins and the RS flanking the V-D and D-J genes, respectively, are sufficient to enforce D gene usage. In this article, we report that in the TCRdelta locus, the Rag proteins are not the major determinant of D gene incorporation. In developing mouse and human thymocytes, the two Ddelta genes rearrange predominantly to form D-D coding joints. In contrast, when tested in ex vivo transfection assays in a nonlymphoid cell line, the flanking RS mediate deletion, rather than incorporation, of the two D genes on both exogenous recombination substrates and the endogenous locus. These results suggest that selective Rag-RS interactions are not the sole regulators of D gene segment incorporation, and additional, perhaps lymphocyte-specific, mechanisms exist that allow proper shaping of the primary AgR repertoire.

subject areas

  • Animals
  • Cell Differentiation
  • Cell Line
  • DNA-Binding Proteins
  • Gene Rearrangement, T-Lymphocyte
  • Genes, T-Cell Receptor delta
  • Genetic Markers
  • Homeodomain Proteins
  • Humans
  • Immunoglobulin Joining Region
  • Immunoglobulin Variable Region
  • Kinetics
  • Mice
  • Mice, Inbred C57BL
  • Nuclear Proteins
  • Protein Sorting Signals
  • Receptors, Antigen, T-Cell, gamma-delta
  • Recombination, Genetic
  • T-Lymphocytes
  • Thymus Gland
  • Transfection
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Identity

International Standard Serial Number (ISSN)

  • 0022-1767

PubMed ID

  • 15879119
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Additional Document Info

start page

  • 6220

end page

  • 6226

volume

  • 174

issue

  • 10

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