Abstract
T cell receptor (TCR) alpha alleles undergo primary and secondary rearrangement in double-positive (DP) thymocytes. By analyzing TCRalpha rearrangement in orphan nuclear receptor RORgamma-deficient mice, in which the DP lifespan is shorter, and in Bcl-x(L)-transgenic mice, in which the DP lifespan is extended, we show that the progression of secondary V(alpha) to J(alpha) rearrangements is controlled by DP thymocyte survival. In addition, because Bcl-x(L) induces a bias towards 3' J(alpha) usage in peripheral T cells, we conclude that the programmed cell death of DP thymocytes is not simply a consequence of failed positive selection. Rather, it limits the progression of rearrangement along the J(alpha) locus and the opportunities for positive selection, thereby regulating the TCRalpha repertoire.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Apoptosis / immunology
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / immunology*
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Cell Differentiation / immunology
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Cell Survival / immunology
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Chromatin / immunology
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DNA / chemistry
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DNA / genetics
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DNA / isolation & purification
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Flow Cytometry
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Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Nuclear Receptor Subfamily 1, Group F, Member 3
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Polymerase Chain Reaction
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / immunology
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Receptors, Antigen, T-Cell, alpha-beta / genetics
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Receptors, Antigen, T-Cell, alpha-beta / immunology*
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Receptors, Cytoplasmic and Nuclear / genetics
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Receptors, Cytoplasmic and Nuclear / immunology*
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Receptors, Retinoic Acid*
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Receptors, Thyroid Hormone*
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Specific Pathogen-Free Organisms
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bcl-X Protein
Substances
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Bcl2l1 protein, mouse
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Chromatin
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Nuclear Receptor Subfamily 1, Group F, Member 3
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Proto-Oncogene Proteins c-bcl-2
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Receptors, Antigen, T-Cell, alpha-beta
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Receptors, Cytoplasmic and Nuclear
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Receptors, Retinoic Acid
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Receptors, Thyroid Hormone
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Rorc protein, mouse
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bcl-X Protein
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DNA