LYMPHOID CELLS IN PRODUCTION OF ANTIBODIES

产生抗体的淋巴细胞

• 批准号: 3115513
• 负责人: G. J THORBECKE
• 金额: $ 25.18万
• 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 1995-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3115513
• 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.

该实验室最近的实验已经建立了快速 IgD 骨髓瘤蛋白 IL-2 或 IL-4 诱导 IgD 受体 (IgD-R) 作用于大部分辅助小鼠 T 细胞和 T 细胞克隆。 CD4+ T 细胞上 IgD-R 的这种表达导致其 抗体产生的辅助活性，可通过细胞转移证明 实验。 IgD 和 IL-4 上调 IgD-R 表达 在年轻小鼠的细胞中取得了成功，但在老年小鼠的细胞中却失败了，而 IL-2 和其他几种药物对任一群体的细胞都有效。 特别令人感兴趣的是初步发现，预孵育 Ca++-离子载体使老年小鼠的 T 细胞对 IgD 产生反应。 这 IgD 导致 T 细胞上 IgD-R 上调的机制将是 研究了蛋白质和 mRNA 合成的需要， 糖基化、细胞内 Ca++ 水平的变化、PKC 活性和 细胞内的易位以及环 AMP 和环 GMP 的激活 依赖性蛋白激酶。此外，磷酸化模式 将研究细胞蛋白质，特别关注 IgD-R 本身的自身磷酸化。 IgD 的任何可检测到的影响 将比较对年轻小鼠细胞的影响与对老年小鼠细胞的影响 老鼠。 细胞膜流动性与细胞膜流动性之间可能存在的关系 将探讨 T 细胞对 IgD 的反应性。 生化 年轻和老年小鼠细胞上 IgD-R 的特征将是 相比之下，细胞释放 IgD 结合因子的能力也会增强 刺激后。 导致 T 上 IgD-R 上调的情况 来自老年小鼠的细胞将被用来增强缺陷 这些小鼠中抗体反应的辅助 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 将作为一种方法进行研究 有助于理解增强辅助功能的机制 T-delta 细胞。 将研究终生 IgD 的影响 a) T 细胞表达 IgD-R 的能力超出 对照小鼠不再做出反应时的年龄，b) 抗体水平 反应，以及 c) 寿命。