LYMPHOID CELLS IN PRODUCTION OF ANTIBODIES

产生抗体的淋巴细胞

• 批准号: 2048932
• 负责人: G. J THORBECKE
• 金额: $ 27.57万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-04-01 至 1995-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2048932
• 关键词: B lymphocyte; CD2 molecule; CD3 molecule; CD4 molecule; age difference; antibody formation; antibody receptor; calcium flux; cell adhesion molecules; cell membrane; cyclic AMP; cyclic GMP; glycosylation; helper T lymphocyte; immunoglobulin D; laboratory mouse; laboratory rabbit; leukocyte adhesion molecules; longevity; messenger RNA; phosphatidylcholines; phospholipase A2; phospholipase D; phosphorylation; protein biosynthesis; protein kinase C; protein transport; radioimmunoassay; second messengers; western blottings

Recent experiments in this laboratory have established the rapid induction by IgD myeloma protein, IL-2 or IL-4, of receptors for IgD (IgD-R) on a large percentage of helper mouse T cells and T cell clones. This expression of IgD-R on CD4+ T cells results in augmentation of their helper activity for antibody production, demonstrable by cell transfer experiments. The upregulation of IgD-R expression with IgD and with IL-4 succeeds with cells from young adult, but not from aged mice, while IL-2 and several other agents are effective with cells from either population. Of particular interest is the preliminary finding that preincubation with a Ca++-ionophore renders T cells from aged mice responsive to IgD. The mechanism by which IgD causes upregulation of IgD-R on T cells will be investigated with respect to the need for protein and mRNA synthesis, glycosylation, intracellular changes in Ca++ levels, PKC activity and translocation in the cells, and activation of cyclic AMP and cyclic GMP dependent protein kinases. In addition, the pattern of phosphorylation of cellular proteins will be studied, with particular attention to autophosphorylation of the IgD-R itself. Any detectable effects of IgD on cells from young mice will be compared with effects on cells from aged mice. The possible relationship between cell membrane fluidity and responsiveness of T cell to IgD will be explored. Biochemical characteristics of IgD-R on cells from young and aged mice will be compared, as will the ability of the cells to release IgD-binding factors after stimulation. Conditions which cause upregulation of IgD-R on T cells from aged mice will be exploited in order to augment the defective helper T cell activity for antibody responses in these mice. Expression of surface antigens CD2, CD3, CD4, LFA1, and ICAM1, as well as of cytokine mRNA in T cells exposed to IgD, will be studied as an approach towards understanding the mechanism of the enhanced helper function of T-delta cells. Studies will be conducted on the effects of lifelong IgD administration on : a) the ability of T cells to express IgD-R beyond the age when control mice no longer respond, b) the level of the antibody responses, and c) longevity.

该实验室的最新实验已经建立了快速 IgD受体IgD骨髓瘤蛋白IL-2或IL-4诱导IgD的诱导 （IGD-R）在很大一部分的辅助小鼠T细胞和T细胞克隆上。 IgD-R在CD4+ T细胞上的表达导致其增强 抗体产生的助手活性，可通过细胞转移证明 实验。 IgD-R表达用IGD和IL-4上调 通过来自年轻成人的细胞成功，而不是来自老年小鼠的细胞，而IL-2 其他几种药物对两个人群的细胞都有效。 特别感兴趣的是初步发现与 Ca ++ - 离子载体使来自对IgD的老年小鼠的T细胞呈现T细胞。 这 IgD引起IGD-R在T细胞上引起IgD-R上调的机制将是 研究了需要蛋白质和mRNA合成的需求， 糖基化，Ca ++水平的细胞内变化，PKC活性和 细胞中的易位，并激活环状AMP和环状GMP 依赖性蛋白激酶。另外，磷酸化的模式 将研究细胞蛋白的细胞蛋白，特别注意 IGD-R本身的自磷酸化。 IGD的任何可检测效应 将年轻小鼠的细胞与对老年细胞的影响进行比较 老鼠。 细胞膜流动性与 将探索T细胞对IgD的响应能力。 生化 IgD-R在年轻小鼠和老年小鼠细胞上的特征将是 比较，细胞释放IgD结合因子的能力也将 刺激后。 导致IGD-R在T上上调的条件 将利用来自老年小鼠的细胞以增加缺陷 这些小鼠的抗体反应的辅助T细胞活性。 表达 表面抗原CD2，CD3，CD4，LFA1和ICAM1以及 暴露于IgD的T细胞中的细胞因子mRNA将作为一种方法研究 要了解增强的辅助功能的机理 T-delta细胞。 将对终身IGD的影响进行研究 给药：a）T细胞表达IGD-R超过超出igd-r的能力 对照小鼠不再响应的年龄，b）抗体的水平 回应和c）长寿。