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未成熟和成熟人类胸腺细胞中T细胞受体Jβ基因片段的使用情况

T-cell receptor J beta gene segment usage in immature and mature human thymocytes.

作者信息

Jeddi-Tehrani M, Hodara V, Esin S, Grunewald J, Wigzell H, Andersson R

机构信息

Microbiology and Tumorbiology Center, Karolinska Institute, Stockholm, Sweden.

出版信息

Scand J Immunol. 1995 Oct;42(4):449-56. doi: 10.1111/j.1365-3083.1995.tb03679.x.

DOI:10.1111/j.1365-3083.1995.tb03679.x
PMID:7569778
Abstract

Immature double positive (DP, CD4+CD8+) and mature single positive (SP, CD4+CD8- and CD4-CD8+) human thymocytes from nine thymi were analysed for their complete patterns of relative TCR J beta multigene member usage in relation to six rearranged V beta family exons (V beta 5.1, 6.1-3, 8, 9, 12 and 18). Each sample tested contained mRNA transcripts corresponding to all potential V beta(D beta)J beta combinations. Individual J beta gene segments were expressed in a similar, highly non-random manner both in SP and DP thymocytes, irrespective of original genomic position of the individual associated V beta exon. In addition, ranges of family usage and frequency of individual over-representations of J beta gene segments, as determined in DP and SP thymocyte populations, displayed no significant differences. Upon comparison of DP and SP thymocytes, however, a discrepancy in one aspect of J beta gene utilization was established: decreasing J beta family 1/J beta family 2 ratios were determined to be positively correlated with increasing maturity of thymocytes, a condition further supported by data previously obtained from studies of PBL T cells. At the individual J beta gene level, the observed gradual modification of the relative family usage can largely be explained by a significant shift from a higher J beta 1.1/J beta 2.7 ratio in DP to a higher J beta 2.7/J beta 1.1 ratio in SP thymocytes. Altogether, the present results imply that selectional processes in the thymus appear to have only minor consequences on the distribution pattern of expressed J beta exons. Hence, the disproportionate pattern of TCR J beta gene usage seems to be established mainly at the recombinatorial level followed by minor adjustments during thymic and post-thymic events.

摘要

分析了来自九个胸腺的未成熟双阳性(DP,CD4 + CD8 +)和成熟单阳性(SP,CD4 + CD8 - 和CD4 - CD8 +)人胸腺细胞,以研究它们与六个重排的Vβ家族外显子(Vβ5.1、6.1 - 3、8、9、12和18)相关的相对TCR Jβ多基因成员使用的完整模式。每个测试样本都包含对应于所有潜在Vβ(Dβ)Jβ组合的mRNA转录本。无论单个相关Vβ外显子的原始基因组位置如何,单个Jβ基因片段在SP和DP胸腺细胞中均以相似的、高度非随机的方式表达。此外,在DP和SP胸腺细胞群体中确定的Jβ基因片段的家族使用范围和个体过度表达频率没有显著差异。然而,在比较DP和SP胸腺细胞时,发现Jβ基因利用的一个方面存在差异:确定Jβ家族1 / Jβ家族2比率的降低与胸腺细胞成熟度的增加呈正相关,先前从PBL T细胞研究中获得的数据进一步支持了这一情况。在单个Jβ基因水平上,观察到的相对家族使用的逐渐变化在很大程度上可以通过从DP中较高Jβ1.1 / Jβ2.7比率到SP胸腺细胞中较高Jβ2.7 / Jβ1.1比率的显著转变来解释。总之,目前的结果表明胸腺中的选择过程似乎对表达的Jβ外显子的分布模式只有轻微影响。因此,TCR Jβ基因使用的不均衡模式似乎主要在重组水平上建立,随后在胸腺和胸腺后事件中进行微小调整。

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