Impact of cellular lifespan on the T cell receptor repertoire

Eur J Immunol. 2007 Jul;37(7):1978-85. doi: 10.1002/eji.200636632.


Pro-survival members of the Bcl-2 family are potent inhibitors of cell death and determine the lifespan of immature thymocytes by counteracting the intrinsically active apoptotic program in these cells. BH3-only proteins are potent antagonists of Bcl-2-like molecules and regulate death and survival of lymphocytes during their development and homeostasis. The intrinsic lifespan of CD4(+)8(+) double-positive thymocytes was reported to actively shape the diversity of the immune repertoire, since mice overexpressing Bcl-x(L) were reported to show a bias towards the usage of distal 3' Jalpha elements 1. To gain support for this concept, we analyzed TCRalpha rearrangements in T lymphocytes that show an extended lifespan due to either loss of the BH3-only protein Bim or overexpression of Bcl-2. A minor but reproducible skewing towards the usage of the more distal 3' Jalpha elements was observed in developing thymocytes and mature T cells from bim(-/-) and vav-bcl-2 transgenic mice, indicating that prolonged survival of double-positive thymocytes does have a significant impact on the selected TCRalpha repertoire. However, the changes that we observed were less pronounced than those found in lck-bcl-x(L) transgenic mice, pointing towards qualitative differences between Bcl-2- and Bcl-x(L)-mediated cell death inhibition during T cell development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / biosynthesis*
  • Bcl-2-Like Protein 11
  • Blotting, Southern
  • Cell Differentiation / immunology
  • Cell Survival / immunology
  • Flow Cytometry
  • Gene Expression Regulation / immunology
  • Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor / genetics*
  • Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor / immunology
  • Membrane Proteins / biosynthesis*
  • Mice
  • Mice, Transgenic
  • Proto-Oncogene Proteins / biosynthesis*
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis*
  • Receptors, Antigen, T-Cell, alpha-beta / genetics*
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes / cytology*


  • Apoptosis Regulatory Proteins
  • Bcl-2-Like Protein 11
  • Bcl2l11 protein, mouse
  • Membrane Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Antigen, T-Cell, alpha-beta