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首页> 外文期刊>Molecular and Cellular Biology >T-cell receptor alpha locus V(D)J recombination by-products are abundant in thymocytes and mature T cells.
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T-cell receptor alpha locus V(D)J recombination by-products are abundant in thymocytes and mature T cells.

机译：T细胞受体α基因座V（D）J重组副产物在胸腺细胞和成熟T细胞中含量很高。

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摘要

In addition to the assembled coding regions of immunoglobulin and T-cell receptor (TCR) genes, the V(D)J recombination reaction can in principle generate three types of by-products in normal developing lymphocytes: broken DNA molecules that terminate in a recombination signal sequence or a coding region (termed signal or coding end molecules, respectively) and DNA molecules containing fused recombination signal sequences (termed reciprocal products). Using a quantitative Southern blot analysis of the murine TCR alpha locus, we demonstrate that substantial amounts of signal end molecules and reciprocal products, but not coding end molecules, exist in thymocytes, while peripheral T cells contain substantial amounts of reciprocal products. At the 5' end of the J alpha locus, 20% of thymus DNA exists as signal end molecules. An additional 30 to 40% of the TCR alpha/delta locus exists as remarkably stable reciprocal products throughout T-cell development, with the consequence that the TCR C delta region is substantially retained in alpha beta committed T cells. The disappearance of the broken DNA molecules occurs in the same developmental transition as termination of expression of the recombination activating genes, RAG-1 and RAG-2. These findings raise important questions concerning the mechanism of V(D)J recombination and the maintenance of genome integrity during lymphoid development.
机译：除了免疫球蛋白和T细胞受体（TCR）基因的组装编码区之外，V（D）J重组反应原则上还可以在正常发育的淋巴细胞中产生三种副产物：终止于重组的破碎DNA分子信号序列或编码区（分别称为信号或编码末端分子）和含有融合重组信号序列的DNA分子（称为互逆产物）。使用鼠TCRα基因座的定量Southern印迹分析，我们证明胸腺细胞中存在大量的信号末端分子和倒数产物，但不存在编码末端分子，而外周T细胞包含大量的倒数产物。在J alpha基因座的5'末端，有20％的胸腺DNA作为信号末端分子存在。在整个T细胞发育过程中，还有30％到40％的TCRα/δ基因座是非常稳定的倒数产物，其结果是TCR Cδ区域基本上保留在αβ定向T细胞中。断裂的DNA分子的消失发生在与重组激活基因RAG-1和RAG-2的表达终止相同的发育过程中。这些发现提出了有关V（D）J重组机制和淋巴发育过程中基因组完整性维持的重要问题。

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