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  • 1
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 163, No. 11 ( 1999-12-01), p. 6053-6059
    Abstract: Pre-TCR expression on developing thymocytes allows cells with productive TCRB gene rearrangements to further differentiate. In wild-type mice, most TCRA gene rearrangements are initiated after pre-TCR expression. However, in pTα-deficient mice, a substantial number of αβ+ thymocytes are still produced, in part because early TCR α-chain expression can rescue immature thymocytes from cell death. In this study, the nature of these TCR α-chains, produced and expressed in the absence of pre-TCR expression, have been analyzed. We show, by FACS analysis and sequencing of rearranged transcripts, that the TCRA repertoire is diverse in pTα−/− mice and that the developmental regulation of AJ segment use is maintained, yet slightly delayed around birth when compared with wild-type mice. We also found that T cell differentiation is more affected by pTα inactivation during late gestation than later in life. These data suggest that the pre-TCR is not functionally required for the initiation and regulation of TCRA gene rearrangement and that fetal thymocytes are more dependent than adult cells on pTα-derived signals for their differentiation.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    RVK:
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    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 1999
    detail.hit.zdb_id: 1475085-5
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  • 2
    In: The Journal of Experimental Medicine, Rockefeller University Press, Vol. 188, No. 12 ( 1998-12-21), p. 2233-2241
    Abstract: VDJ recombination of T cell receptor and immunoglobulin loci occurs in immature lymphoid cells. Although the molecular mechanisms of DNA cleavage and ligation have become more clear, it is not understood what controls which target loci undergo rearrangement. In interleukin 7 receptor (IL-7R)α−/− murine thymocytes, it has been shown that rearrangement of the T cell receptor (TCR)-γ locus is virtually abrogated, whereas other rearranging loci are less severely affected. By examining different strains of mice with targeted mutations, we now observe that the signaling pathway leading from IL-7Rα to rearrangement of the TCR-γ locus requires the γc receptor chain and the γc-associated Janus kinase Jak3. Production of sterile transcripts from the TCR-γ locus, a process that generally precedes rearrangement of a locus, was greatly repressed in IL-7Rα−/− thymocytes. The repressed transcription was not due to a lack in transcription factors since the three transcription factors known to regulate this locus were readily detected in IL-7Rα−/− thymocytes. Instead, the TCR-γ locus was shown to be methylated in IL-7Rα−/− thymocytes. Treatment of IL-7Rα−/− precursor T cells with the specific histone deacetylase inhibitor trichostatin A released the block of TCR-γ gene rearrangement. This data supports the model that IL-7R promotes TCR-γ gene rearrangement by regulating accessibility of the locus via demethylation and histone acetylation of the locus.
    Type of Medium: Online Resource
    ISSN: 0022-1007 , 1540-9538
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    Language: English
    Publisher: Rockefeller University Press
    Publication Date: 1998
    detail.hit.zdb_id: 1477240-1
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