T cell development in TCR beta enhancer-deleted mice: Implications for alpha beta T cell lineage commitment and differentiation

T cell differentiation in the mouse thymus is an intricate, highly coordina ted process that requires the assembly of TCR complexes from individual com ponents, including those produced by the precisely timed V(D)J recombinatio n of TCR genes. Mice carrying a homozygous deletion of the TCR beta transcr iptional enhancer (E beta) demonstrate an inhibition of V(D)J recombination at the targeted TCR beta locus and a block in alpha beta T cell differenti ation. In this study, we have characterized the T cell developmental defect s resulting from the E beta(-/-) mutation, in light of previously reported results of the analyses of TCR beta-deficient (TCR beta(-/-)) mice. Similar to the latter mice, production of TCR beta chains is abolished in the E be ta(-/-) animals, and under these conditions differentiation into cell-surfa ce TCR-, CD4(+)CD8(+) double positive (DP) thymocytes depends essentially o n the cell-autonomous expression of TCR delta-chains and, most likely, TCR gamma-chains. However, contrary to previous reports using TCR beta(-/-) mic e, a minor population of TCR gamma delta(+) DP thymocytes was found within the E beta(-/-) thymi, which differ in terms of T cell-specific gene expres sion and V(D)J recombinase activity, from the majority of TCR-, alpha beta lineage committed DP thymocytes. We discuss these data with respect to the functional role of E beta in driving alpha beta T cell differentiation and the mechanism of alpha beta T lineage commitment.