Bogue M, Candéias S, Benoist C, Mathis D
Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Strasbourg, France.
EMBO J. 1991 Dec;10(12):3647-54. doi: 10.1002/j.1460-2075.1991.tb04931.x.
According to several functional criteria, the mature thymocytes of neonatal and adult mice are distinctly different. We wondered whether these differences in function might have a structural correlate: do neonates have a distinct repertoire of alpha:beta T cells? In this study, we have exploited the power of polymerase chain reaction technology to generate large numbers of T cell receptor sequences from sorted thymocyte populations from newborn and adult mice. The newborn-derived sequences show very few N nucleotide additions, usually the major source of diversity in T cell receptors. Most interestingly, the paucity of N insertions appears to be exaggerated by selection events that operate during T cell differentiation in the thymus. The significance of these results is largely: (i) that they parallel recent findings on the B cell repertoire in neonates, raising questions about the reactivities specified by such a special repertoire; and (ii) that they suggest a means to 'tag' T cells exported perinatally, allowing one to test the premise that autoreactive T cells derive preferentially from the newborn repertoire.
根据多项功能标准,新生小鼠和成年小鼠的成熟胸腺细胞明显不同。我们想知道这些功能上的差异是否可能存在结构上的关联:新生儿是否拥有独特的α:β T细胞库?在本研究中,我们利用聚合酶链反应技术的强大功能,从新生小鼠和成年小鼠分选的胸腺细胞群体中生成大量T细胞受体序列。源自新生小鼠的序列显示出极少的N核苷酸添加,而N核苷酸添加通常是T细胞受体多样性的主要来源。最有趣的是,在胸腺中T细胞分化过程中起作用的选择事件似乎加剧了N插入的缺乏。这些结果的重要意义主要在于:(i)它们与最近关于新生儿B细胞库的发现相似,引发了关于这种特殊库所指定的反应性的问题;(ii)它们提出了一种“标记”围产期输出的T细胞的方法,从而使人们能够检验自身反应性T细胞优先源自新生儿库这一前提。