LYMPHOCYTE-T DEVELOPMENT IN SCID MICE IS ARRESTED SHORTLY AFTER THE INITIATION OF T-CELL RECEPTOR DELTA-GENE RECOMBINATION
LYMPHOCYTE-T DEVELOPMENT IN SCID MICE IS ARRESTED SHORTLY AFTER THE INITIATION OF T-CELL RECEPTOR DELTA-GENE RECOMBINATION
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DOI：
10.1101/gad.5.8.1357
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发表时间：
1991-08-01
影响因子：
10.5
通讯作者：
BOSMA, MJ
中科院分区：
文献类型：
--
作者：
CARROLL, AM;BOSMA, MJ
Scid小鼠缺乏功能性淋巴细胞，因为它们携带一种突变，损害免疫球蛋白和t细胞受体（TCR）基因的重排。在胸腺细胞和胸腺细胞杂交瘤的DNA中，常规观察到tcr - δ基因重排，而不是γ和β基因重排。TCR δ基因重排似乎只涉及d - δ -1、d - δ -2和j - δ -1元件；未观察到D-delta-1上游元件（如V-delta-1）的重排，并且在scid胸腺细胞的RNA中未检测到与完全组装的tcr -delta基因（VDJ-delta或VDDJ-delta）对应的转录本。这些发现表明，d - δ -1、d - δ -2和j - δ -1可能是第一批经历重组的TCR基因元件，并且scid t系细胞在分化阶段或分化后不久发育受阻。采用聚合酶链反应（PCR）扩增了一类TCR-delta重组片段（D-delta-2-J-delta-1）并进行了克隆，并对其重组连接进行了测序。大部分片段显示正常的编码关节。有趣的是，缺少N个插入的7个编码关节中有5个显示同源序列短片段（2-3 bp）之间重组的证据。如前所述，尽管存在正常的d - δ -2- j - δ -1重排，但普遍缺乏v - δ -、j - γ -和j - β相关重排，这提高了scid突变可能导致TCR基因重组过早停止的可能性，从而阻止了早期t细胞的发育。
Scid mice lack functional lymphocytes because they carry a mutation that impairs rearrangement of immunoglobulin and T-cell receptor (TCR) genes. Rearrangement of TCR-delta, but not gamma and beta-genes, was routinely observed in DNA of scid thymocytes and thymocyte hybridomas. TCR delta-gene rearrangements appeared to involve D-delta-1, D-delta-2, and J-delta-1 elements only; rearrangement of elements upstream of D-delta-1 (e.g., V-delta-1) was not observed, and transcripts corresponding to fully assembled TCR-delta-genes (VDJ-delta or VDDJ-delta) were not detected in RNA from scid thymocytes. These findings suggest that D-delta-1, D-delta-2, and J-delta-1 may be among the first TCR gene elements to undergo recombination and that scid T-lineage cells are developmentally arrested during or shortly after this stage of differentiation. One class of TCR-delta recombination fragments (D-delta-2-J-delta-1) was amplified by the polymerase chain reaction (PCR) and cloned, and the recombination junctions were sequenced. Most fragments showed normal coding joints. Interestingly, five of seven coding joints that lacked N insertions showed evidence of recombination between short stretches (2-3 bp) of homologous sequence. As discussed, the general absence of V-delta-, J-gamma-, and J-beta-associated rearrangements, despite the occurrence of normal D-delta-2-J-delta-1 rearrangements, raises the possibility that the scid mutation may cause premature cessation of TCR gene recombination and thereby arrest early T-cell development.