REGULATION OF LYMPHOCYTE ACTIVATION AND PROLIFERATION

迄今为止研究的所有细胞都需要转铁蛋白才能生长。 我们和 其他人已经证明转铁蛋白受体的抗体 阻断淋巴母细胞样细胞系的生长。 在有丝分裂原中- 刺激淋巴细胞，这些抗体阻断增殖。 我们 正在研究调节这些细胞出现的过程， 淋巴细胞和淋巴母细胞样细胞系中的受体， 这些受体在细胞生长和代谢中的功能。 我们 已经证明G1期阻滞发生在正常和 当转铁蛋白受体被阻断时，即使 细胞表达高水平的生长因子受体 信使RNA和c-myc和c-myb信使RNA。 此外，无论是阻断钙通道还是添加 cAMP进入细胞导致G1期阻滞和转铁蛋白受体丧失 mRNA。 cAMP的作用可以在 转录。 我们已经开始研究核蛋白在 T细胞从G 0期到S期的转变。 在一项初步研究中，一个C- myc反义寡聚体完全阻断了c- myc蛋白在有丝分裂原处理的T细胞中，然而这些细胞继续 表达IL-2受体、转铁蛋白受体和DNA聚合酶 α蛋白 然而，他们未能合成DNA。 我们计划 继续使用针对各种核蛋白的反义构建体， 研究它们在细胞生长和活化中的作用。 最初，我们 研究DNA中几种核蛋白的需求 聚合酶α活性。 到目前为止，我们已经确定， 这些蛋白质，c-myc和Ki-67，是聚合酶α所必需的， 体外活性。

All cells studied to date require transferrin for growth. We and others have shown that antibodies to the transferrin receptor block the growth of lymphoblastoid cell lines. In mitogen- stimulated lymphocytes, these antibodies block proliferation. We are studying the processes which regulate the appearance of these receptors in lymphocytes and lymphoblastoid cell lines, and the function of these receptors in cell growth and metabolism. We have demonstrated that G1 arrest occurs in both normal and malignant cells when transferrin receptors are blocked, even if cells are expressing high levels of growth factor receptor messenger RNA and c-myc and c-myb messenger RNA. Furthermore, either blockage of calcium channels or addition of cAMP to cells results in G1 arrest and loss of transferrin receptor mRNA. The effect of cAMP can be detected at the level of transcription. We have begun to study the role of nuclear proteins in the transition of T cells from G0 to S phase. In an initial study, a c- myc antisense oligomer completely blocked the appearance of c- myc protein in mitogen treated T cells, yet these cells went on to express IL-2 receptors, transferrin receptors and DNA polymerase alpha protein. Yet they failed to synthesize DNA. We plan to continue to use antisense constructs to various nuclear proteins to study their role(s) in cell growth and activation. Initially, we are examining the requirements for several nuclear proteins in DNA polymerase alpha activity. To date, we have determine that two such proteins, c-myc and Ki-67, are required for polymerase alpha activity in vitro.