Konno Akihiro, Wada Taizo, Schurman Shepherd H, Garabedian Elizabeth K, Kirby Martha, Anderson Stacie M, Candotti Fabio
Disorders of Immunity Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, 49 Convent Dr, 49/3A20, Bethesda, MD 20892, USA.
Blood. 2004 Jan 15;103(2):676-8. doi: 10.1182/blood-2003-05-1739. Epub 2003 Sep 22.
Somatic mosaicism because of in vivo reversion has been recently reported in a small number of patients affected with Wiskott-Aldrich syndrome (WAS). Flow cytometry analysis of WAS protein (WASP) expression has shown that these patients carried revertant cells only among T lymphocytes. Here, we have used high-resolution capillary electrophoresis to analyze genomic DNA from highly purified cells of one of these patients and detected revertant sequences also within the B-cell fraction. The demonstration of revertant cells among both T and B lymphocytes in this patient is consistent with the reversion event having occurred in a common lymphoid progenitor. However, although WASP-expressing T cells showed selective advantage and were readily detectable in the periphery of the mosaic patient, revertant B lymphocytes remained below the detection threshold of flow cytometry. These findings suggest that, contrary to T cells, differentiation and survival of B lymphocytes is minimally dependent on WASP.
最近有报道称，一小部分患有威斯科特-奥尔德里奇综合征（WAS）的患者因体内回复突变而出现体细胞嵌合现象。对WAS蛋白（WASP）表达进行的流式细胞术分析表明，这些患者仅在T淋巴细胞中携带回复细胞。在此，我们使用高分辨率毛细管电泳分析了其中一名患者高度纯化细胞的基因组DNA，并在B细胞部分也检测到了回复序列。该患者T淋巴细胞和B淋巴细胞中均存在回复细胞，这与回复事件发生在共同淋巴祖细胞中的情况一致。然而，尽管表达WASP的T细胞显示出选择性优势，并且在嵌合患者的外周血中易于检测到，但回复性B淋巴细胞仍低于流式细胞术的检测阈值。这些发现表明，与T细胞相反，B淋巴细胞的分化和存活对WASP的依赖性极小。
