TCR gene recombination and alpha beta-gamma delta lineage divergence: productive TCR-beta rearrangement is neither exclusive nor preclusive of gamma delta cell development.
TCR gene recombination and alpha beta-gamma delta lineage divergence: productive TCR-beta rearrangement is neither exclusive nor preclusive of gamma delta cell development.
复制标题
DOI：
10.4049/jimmunol.157.10.4293
复制
发表时间：
1996-11
影响因子：
4.4
通讯作者：
Douglas B. Burtrum;S. Kim;E. Dudley;A. Hayday;H. Petrie
中科院分区：
文献类型：
--
作者：
Douglas B. Burtrum;S. Kim;E. Dudley;A. Hayday;H. Petrie
胸腺内可产生两种类型的T淋巴细胞，通过tcr - γ δ或- α β表面表达来区分。这些细胞胸腺内分化的调控尚不清楚，至少部分原因是胸腺源性γ δ细胞很少被研究。我们利用定量Southern blotting、pcr克隆/测序和限制性片段长度多态性分析了胸腺源性γ δ细胞中tcr - α和- β基因的重组。我们发现tcr - β基因重组在胸腺γ δ细胞中经常发生。此外，不仅完全的（V-D-J） tcr - β基因重排发生在胸腺γ δ细胞中，而且帧内重排的频率比基于随机发生的预测要高。相反，我们发现胸腺衍生的伽马δ细胞不会对tcr - α位点进行可检测的重排。这些研究清楚地界定了在tcr - β之后和tcr - α基因重组之前胸腺中α - β和γ - δ的作用。此外，虽然我们的数据支持作为成功的tcr - γ和- δ基因重排的结果的伽马δ谱系承诺，但我们没有发现对谱系承诺的竞争模型的支持，因为有效的tcr - β基因重排并不一定会使细胞降级到α - β谱系。
Two types of T lymphocytes can be generated intrathymically, distinguishable by either TCR-gamma delta or -alpha beta surface expression. Regulation of the intrathymic divergence of these cells is unresolved, at least in part because thymically derived gamma delta cells have rarely been studied. We used quantitative Southern blotting together with PCR-based cloning/sequencing and restriction fragment length polymorphism to analyze TCR-alpha and -beta gene recombination in thymically derived gamma delta cells. We found that TCR-beta gene recombination is a frequent occurrence in thymic gamma delta cells. Furthermore, not only do complete (V-D-J) TCR-beta gene rearrangements occur in thymic gamma delta cells, but the frequency of in-frame rearrangements is greater than would be predicted based upon random occurrence. In contrast, we show that thymically derived gamma delta cells do not make detectable rearrangements of the TCR-alpha locus. These studies clearly demarcate a point for alpha beta vs gamma delta commitment in the thymus, after TCR-beta but before TCR-alpha gene recombination. Further, while our data support gamma delta lineage commitment as a consequence of successful TCR-gamma and -delta gene rearrangement, we do not find support for a competitive model of lineage commitment, since productive TCR-beta gene rearrangement does not necessarily relegate cells to the alpha beta lineage.