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Early Expression of a Functional TCR Chain Inhibits TCR Gene Rearrangements without Altering the Frequency of TCR Lineage Cells¹

David Gerber^*, Laurent Boucontet and Pablo Pereira^2,

^* Howard Hughes Medical Institute, Institute of Physical and Chemical Research/Neuroscience Research Center, The Picower Center for Learning and Memory, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139; and Unité du Développement des Lymphocytes, Centre National de la Recherche Scientifique, Unité de Recherche Associée 1961, Institut Pasteur, Paris, France

To investigate the consequences of the simultaneous expression in progenitor cells of a TCR and a pre-TCR on / lineage commitment, we have forced expression of functionally rearranged TCR, TCR, and TCR chains by means of transgenes. Mice transgenic for the three TCR chains contain numbers of thymocytes comparable to those of mice transgenic for both TCR and TCR chains, and numbers of thymocytes similar to those found in mice solely transgenic for a rearranged TCR chain gene. T cells from the triple transgenic mice express the transgenic TCR chain, but do not express a TCR chain, and, by a number of phenotypic and molecular parameters, appear to be bona fide thymocytes. Our results reveal a remarkable degree of independence in the generation of and lineage cells from progenitor cells that, in theory, could simultaneously express a TCR and a pre-TCR.