EVIDENCE THAT PRODUCTIVE REARRANGEMENTS OF TCR-GAMMA GENES INFLUENCE THE COMMITMENT OF PROGENITOR CELLS TO DIFFERENTIATE INTO ALPHA-BETA OR GAMMA-DELTA T-CELLS

被引:46
作者
KANG, J
BAKER, J
RAULET, DH
机构
[1] UNIV CALIF BERKELEY,DEPT MOLEC & CELL BIOL,DIV IMMUNOL,BERKELEY,CA 94720
[2] UNIV CALIF BERKELEY,CANC RES LAB,BERKELEY,CA 94720
关键词
T CELL DEVELOPMENT; T CELL LINEAGE DECISION; T CELL RECEPTOR GAMMA GENE REARRANGEMENT; T CELL RECEPTOR GAMMA TRANSGENIC MICE;
D O I
10.1002/eji.1830250946
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:2706 / 2709
页数:4
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