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European Journal of Immunology
Article . 2007 . Peer-reviewed
License: Wiley Online Library User Agreement
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Impact of cellular lifespan on the T cell receptor repertoire

Authors: Abdelbasset, Hamrouni; Anna, Olsson; G Jan, Wiegers; Andreas, Villunger;

Impact of cellular lifespan on the T cell receptor repertoire

Abstract

AbstractPro‐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‐xL were reported to show a bias towards the usage of distal 3′ Jα elements 1. To gain support for this concept, we analyzed TCRα 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′ Jα 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 TCRα repertoire. However, the changes that we observed were less pronounced than those found in lck‐bcl‐xL transgenic mice, pointing towards qualitative differences between Bcl‐2‐ and Bcl‐xL‐mediated cell death inhibition during T cell development.

Keywords

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

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
8
Average
Average
Top 10%
bronze