REGULATION OF RECEPTORS ON T-LYMPHOCYTES

B细胞和T细胞起源于共同的前体，这表明， 在基因的转录调控中重叠，特别是那些 表达后不久，分歧的两个血统。 的因素分析 调节早期淋巴基因的表达， 导致B和T细胞分化的信号。 TCR β基因在T细胞个体发育早期表达， 免疫球蛋白μ重链基因的调控特征。 IL- 2 R α基因在T细胞活化时通过序列元件被诱导 与NF-kB结合位点同源，最初在 免疫球蛋白k轻链基因增强子。 的近期目标 本申请中概述的实验是为了定义（通过转染和 转基因小鼠分析）所需的序列元件， TCR-β和IL-2 R α基因的表达，并随后鉴定 与这些序列相互作用的反式作用因子。 这些研究 有望使我们在探测淋巴发育方面处于有利地位 通过识别在基因启动或关闭中起关键作用的因素， B和T细胞发育的不同阶段。

Origin of B and T cells from a common precursor suggests that there might be overlap in the transcriptional regulation of genes, particularly those expressed soon after divergence of the 2 lineages. Analysis of factors regulating early lymphoid gene expression should provide insights into the signals leading to B and T cell differentiation. The TCR beta gene is expressed early during T cell ontogeny and may share regulatory features with the immunoglobulin mu heavy chain gene. The IL- 2Ralpha gene is induced upon T cell activation via a sequence element homologous to the NF-kB binding site, originally identified in the immunoglobulin k light chain gene enhancer. The immediate goals of the experiments outlined in this application are to define (by transfection and transgenic mouse analysis) the sequence elements required for appropriate expression of the TCR-beta and IL-2Ralpha genes and subsequently identified the trans-acting factors interacting with these sequences. These studies are expected to place us in a strong position to probe lymphoid development by identifying factors that are critical in turning genes on or off at different stages of B and T cell development.