Evidence that productive rearrangements of TCR gamma genes influence the commitment of progenitor cells to differentiate into alpha beta or gamma delta T cells.
Two models have been considered to account for the differentiation of gamma delta and alpha beta T cells from a common hematopoietic progenitor cell. In one model, progenitor cells commit to a lineage before T cell receptor (TCR) rearrangement occurs. In the other model, progenitor cells first undergo rearrangement of TCR gamma, delta, or both genes, and cells that succeed in generating a functional receptor commit to the gamma delta lineage, while those that do not proceed to attempt complete beta and subsequently alpha gene rearrangements. A prediction of the latter model is that TCR gamma rearrangements present in alpha beta T cells will be nonproductive. We tested this hypothesis by examining V gamma 2-J gamma 1C gamma 1 rearrangements, which are commonly found in alpha beta T cells. The results indicate that V gamma 2-J gamma 1C gamma 1 rearrangements in purified alpha beta T cell populations are almost all nonproductive. The low frequency of productive rearrangements of V gamma 2 in alpha beta T cells is apparently not due to a property of the rearrangement machinery, because a transgenic rearrangement substrate, in which the V gamma 2 gene harbored a frame-shift mutation that prevents expression at the protein level, was often rearranged in a productive configuration in alpha beta T cells. The results suggest that progenitor cells which undergo productive rearrangement of their endogenous V gamma 2 gene are selectively excluded from the alpha beta T cell lineage.
Kang
J
J
Department of Molecular and Cell Biology, University of California, Berkeley, 94720, USA.
Baker
J
J
Raulet
D H
DH
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics* / Q000276:immunology; D013234:Stem Cells / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta