LYMPHOID CELLS IN PRODUCTION OF ANTIBODIES

这个实验室最近的实验已经建立了快速的 IGD骨髓瘤蛋白IL-2或IL-4诱导的IGD受体 (IGD-R)在很大比例的辅助小鼠T细胞和T细胞克隆上。 这种在CD4+T细胞上的IGD-R的表达导致它们的 产生抗体的辅助活性，可通过细胞转移来证明 实验。IGD和IL-4对IGD-R表达的上调作用 成功地使用了来自年轻成年鼠的细胞，但不是来自老龄鼠的细胞，而IL-2 其他几种药物对这两个群体的细胞都有效。 特别令人感兴趣的是，初步发现与 钙离子载体使老年小鼠的T细胞对IGD产生反应。这个 IGD导致T细胞上IGD-R上调的机制将是 关于蛋白质和信使核糖核酸合成的需求的研究， 糖基化，细胞内钙离子水平的变化，PKC活性和 细胞内转位与环磷酸腺苷和环鸟苷的激活 依赖的蛋白激酶。此外，磷酸化的模式 将对细胞蛋白进行研究，特别注意 IGD-R自身的自动磷酸化。IGD的任何可检测到的影响 对幼鼠细胞的影响将与对老年细胞的影响进行比较 老鼠。细胞膜流动性与细胞膜流动性的可能关系 我们将探讨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 与之相比，细胞释放IGD结合因子的能力也会更强 在刺激之后。引起T细胞IGD-R上调的条件 将利用老龄小鼠的细胞来增加有缺陷的小鼠 这些小鼠抗体反应的辅助性T细胞活性。表达式 表面抗原CD2、CD3、CD4、LFA1和ICAM1以及 作为一种方法，将研究暴露于IGD的T细胞中的细胞因子mRNA 向理解增强的帮手功能的机制迈进 T-Delta细胞。将对终生IGD的影响进行研究 给药：a)T细胞表达IGD-R的能力超过 对照组小鼠不再有反应的年龄，b)抗体水平 回应，以及c)长寿。

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.