DEVELOPMENTAL REGULATION AND FUNCTIONAL CAPACITY OF FETAL LYMPHOCYTES

有几条证据表明，淋巴细胞在 胎儿的生命代表了不同于 那些在成虫体内产生的。胎儿淋巴组织似乎 只在胎儿时期发育，就像成人造血干细胞一样 失去了产生胎儿淋巴细胞的能力。潜在的 参与建立这些胎儿的分子机制 血统目前尚不清楚，但可能反映了差异 特定转录因子的表达。我们目前所了解的 早期淋巴细胞特异性基因表达的调节是衍生出来的 主要来自对永生化细胞系的研究，这些细胞系几乎没有 与正常发育的淋巴样细胞相似。因此，几乎没有 或者对控制这些基因的机制一无所知 在正常分化细胞中。 除了发育阶段有明显差异外，胎儿 淋巴细胞在其免疫受体上表现出的多样性不如他们的 成年对应者，并在一生中表现出特定的行为。 后一种差异表明胎儿淋巴样细胞 产生是为了实现一种独特的功能。定义为胎儿淋巴组织 前身尚未可用，其发展潜力 这些细胞和胎儿免疫系统的功能是由 它们还没有被定义。 胎儿淋巴前体现在可以从 多能干细胞。因此，工作已成为可能 淋巴前体的分析不会被 干细胞分化的贡献。这项提案的目标是 是为了研究特定转录因子在基因转录中的作用 胎儿淋巴系群体的建立和定义 这些细胞在动物体内的功能。

Several lines of evidence suggest that lymphocytes generated during fetal life represent a distinct subpopulation of cells that differ from those produced in the adult. Fetal lymphoid populations seem to develop only during fetal life as adult hematopoietic stem cells have lost the capacity to give rise fetal lymphocytes. The underlying molecular mechanisms involved in the establishment of these fetal lineages are currently not known, but likely reflect differential expression of specific transcription factors. Our current knowledge of the regulation of early lymphocyte-specific gene expression is derived largely from studies on immortalized cell lines that bear little resemblance to normal developing lymphoid cells. Consequently little or nothing is known concerning mechanisms that govern these genes in normal differentiating cells. In addition to the obvious difference in the development stage, fetal lymphocytes show less diversity in their immune receptors than their adult counterparts and exhibit specific behaviors throughout life. These latter differences suggest that fetal lymphoid cells are generated to fulfill a unique function. As defined fetal lymphoid precursors have not been available, the developmental potential of these cells and the function of a fetal immune system generated from them have not been defined. Fetal lymphoid precursors can now been fractionated from mulipotent stem cells. Therefore, it has become possible to work with lymphoid precursors whose analysis will not be obscured by the contribution of differentiating stem cells. The goals of this proposal are to investigate the role of specific transcription factors in the establishment of the fetal lymphoid populations and to define the function of these cells in the animal.