Two waves of recombinase gene expression in developing thymocytes

doi:10.1084/jem.179.4.1355

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Two waves of recombinase gene expression in developing thymocytes

A Wilson, W Held and HR MacDonald
Ludwig Institute for Cancer Research, Lausanne Branch, Epalinges, Switzerland.

During T cell development in the thymus, T cell receptor (TCR) alpha, beta, gamma, and delta genes are rearranged and expressed. TCR rearrangement strictly depends upon the coordinate activity of two recombinase activating genes, Rag-1 and Rag-2. In this study we have followed the expression of these genes at different stages of intrathymic development. The results indicate that there are two periods of high Rag-1 and Rag-2 mRNA expression. The first wave peaks early at the CD25+CD4-CD8-CD3- stage of development and coincides with the initial appearance of transcripts derived from fully rearranged TCR beta, gamma, and delta genes, whereas the second wave occurs later at the CD4+CD8+ stage coincident with full-length TCR alpha mRNA expression. Active downregulation of Rag-1 and Rag-2 mRNA expression appears to occur in vivo between the two peaks of recombinase activity. This phenomenon can be mimicked in vitro in response to artificial stimuli such as phorbol myristate acetate and calcium ionophore. Collectively our data suggest that recombinase expression is actively regulated during early thymus development independently of cell surface expression of a mature heterodimeric TCR protein complex.
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Monroe, R. J., Chen, F., Ferrini, R., Davidson, L., Alt, F. W. (1999). RAG2 is regulated differentially in B and T cells by elements 5' of the promoter. Proc. Natl. Acad. Sci. USA 96: 12713-12718 [Abstract] [Full Text]
Wilson, A., Capone, M., MacDonald, H. R. (1999). Unexpectedly late expression of intracellular CD3{epsilon} and TCR {gamma}{delta} proteins during adult thymus development. Int Immunol 11: 1641-1650 [Abstract] [Full Text]
Carleton, M., Ruetsch, N. R., Berger, M. A., Rhodes, M., Kaptik, S., Wiest, D. L. (1999). Signals Transduced by CD3{epsilon}, But Not by Surface Pre-TCR Complexes, Are Able to Induce Maturation of an Early Thymic Lymphoma In Vitro. J. Immunol. 163: 2576-2585 [Abstract] [Full Text]
Baldwin, K. K., Trenchak, B. P., Altman, J. D., Davis3, M. M. (1999). Negative Selection of T Cells Occurs Throughout Thymic Development. J. Immunol. 163: 689-698 [Abstract] [Full Text]
Zhong, X.-P., Krangel, M. S. (1999). Enhancer-Blocking Activity Within the DNase I Hypersensitive Site 2 to 6 Region Between the TCR {alpha} and Dad1 Genes. J. Immunol. 163: 295-300 [Abstract] [Full Text]
Lauring, J., Schlissel, M. S. (1999). Distinct Factors Regulate the Murine RAG-2 Promoter in B- and T-Cell Lines. Mol. Cell. Biol. 19: 2601-2612 [Abstract] [Full Text]
Trigueros, C., Ramiro, A. R., Carrasco, Y. R., de Yebenes, V. G., Albar, J. P., Toribio, M. L. (1998). Identification of a Late Stage of Small Noncycling pTalpha - �Pre-T Cells as Immediate Precursors of T Cell Receptor alpha /beta + �Thymocytes. JEM 188: 1401-1412 [Abstract] [Full Text]
Laky, K., Lefrancois, L., von Freeden-Jeffry, U., Murray, R., Puddington, L. (1998). The Role of IL-7 in Thymic and Extrathymic Development of TCR{gamma}{delta} Cells. J. Immunol. 161: 707-713 [Abstract] [Full Text]
Wang, H., Diamond, R. A., Rothenberg, E. V. (1998). Cross-lineage expression of Ig-beta (B29) in thymocytes: Positive and negative gene regulation to establish T cell identity. Proc. Natl. Acad. Sci. USA 95: 6831-6836 [Abstract] [Full Text]
Utting, O., Teh, S.-J., Teh, H.-S. (1998). T Cells Expressing Receptors of Different Affinity for Antigen Ligands Reveal a Unique Role for p59fyn in T Cell Development and Optimal Stimulation of T Cells by Antigen. J. Immunol. 160: 5410-5419 [Abstract] [Full Text]
Auphan, N., Simon, A. K., Asnagli, H., Phillips, R. J., Rincon, M., Ghosh, S., Flavell, R. A., Schmitt-Verhulst, A.-M. (1998). Consequences of Intrathymic TCR Engagement by Partial Agonist on Selection Events and Peripheral T Cell Activation Program. J. Immunol. 160: 4810-4821 [Abstract] [Full Text]
Livak, F., Schatz, D. G. (1998). Alternative splicing of rearranged T cell receptor delta �sequences to the constant region of the alpha �locus. Proc. Natl. Acad. Sci. USA 95: 5694-5699 [Abstract] [Full Text]
Gaffney, P. M., Lund, J., Miller, J. S. (1998). FLT-3 Ligand and Marrow Stroma-Derived Factors Promote CD3gamma , CD3delta , CD3zeta , and RAG-2 Gene Expression in Primary Human CD34+LIN-DR- Marrow Progenitors. Blood 91: 1662-1670 [Abstract] [Full Text]
Chattopadhyay, S., Whitehurst, C. E., Schwenk, F., Chen, J. (1998). Biochemical and Functional Analyses of Chromatin Changes at the TCR-{beta} Gene Locus During CD4-CD8- to CD4+CD8+ Thymocyte Differentiation. J. Immunol. 160: 1256-1267 [Abstract] [Full Text]
Zhong, X.-P., Krangel, M. S. (1997). An enhancer-blocking element between alpha �and delta �gene segments within the human T cell receptor alpha /delta �locus. Proc. Natl. Acad. Sci. USA 94: 5219-5224 [Abstract] [Full Text]
Lauzurica, P., Zhong, X.-P., Krangel, M. S., Roberts, J. L. (1997). Regulation of �T Cell Receptor delta �Gene Rearrangement by CBF/PEBP2. JEM 185: 1193-1202 [Abstract] [Full Text]
Bruno, L., Res, P., Dessing, M., Cella, M., Spits, H. (1997). Identification of a Committed T Cell Precursor Population in Adult Human Peripheral Blood. JEM 185: 875-884 [Abstract] [Full Text]
Roberts, J. L., Lauzurica, P., Krangel, M. S. (1997). Developmental Regulation of �VDJ Recombination By the Core Fragment of the T Cell Receptor alpha �Enhancer. JEM 185: 131-140 [Abstract] [Full Text]
Falk, I., Biro, J., Kohler, H., Eichmann, K. (1996). Proliferation Kinetics Associated with T Cell Receptor-beta Chain Selection of Fetal Murine Thymocytes. JEM 184: 2327-2340 [Abstract] [Full Text]
Hoffman, E S, Passoni, L, Crompton, T, Leu, T M, Schatz, D G, Koff, A, Owen, M J, Hayday, A C (1996). Productive T-cell receptor beta-chain gene rearrangement: coincident regulation of cell cycle and clonality during development in vivo.. Genes Dev. 10: 948-962 [Abstract]
Bogue, M A, Zhu, C, Aguilar-Cordova, E, Donehower, L A, Roth, D B (1996). p53 is required for both radiation-induced differentiation and rescue of V(D)J rearrangement in scid mouse thymocytes.. Genes Dev. 10: 553-565 [Abstract]