GROWTH/DIFFERENTIATION FACTORS IN NORMAL/IMMUNE B CELLS

共同变异型患者的B细胞 泛丙种球蛋白血症天生不能成熟到 高比例抗体分泌细胞以正常速度分泌，即使在 存在正常的相互作用的T细胞和单核细胞。然而， 他们能够完成某些早期和中期的工作 激活事件正常，因此无法激活 这似乎不是他们的问题。预料到识别出 来自不同患者的B细胞缺陷步骤将揭示许多 关于正常的B细胞激活，我们最近提出了开发 描述了使用因子或 与表面Ig交联剂或在表面Ig交联剂之后作用以促进 进展为DNA合成或抗体分泌。这些 实验应区分有缺陷的患者 与增殖缺陷患者的鉴别。一个 潜在重要的新方法是分析如何 细胞松弛素，它阻止肌动蛋白组装成微丝， 促进DNA合成的进展，以及他们是否能做到 因此，在正常机制被阻断的患者中。最后， 使用多种方法检测早期生化和细胞表面 在激活事件时，我们会发现是否存在差异化 干扰素β2，高、低分子量B细胞 生长因子和抗CDw40利用任何已知信号 转导途径或刺激中间事件，所以我们 还可以确定他们的信号在有缺陷的B中进展了多远 细胞。这种方法具有阐明正常的双重目标 B细胞在生化上的分化和增殖信号 水平，并了解有缺陷的B的生理 细胞，最终导致新的调控策略 抗体的产生。

B cells from patients with common variable panhypogammaglobulinemia are intrinsically unable to mature to high-rate antibody-secreting cells at the normal pace even in the presence of normal interacting T cells and monocytes. However, they are able to perform certain early and intermediate activation events normally, so failure to become activated appears not to be their problem. Anticipating that identifying the defective step in B cells from different patients will reveal much about normal B cell activation, we propose to exploit recently described alternative modes of activating B cells with factors or reagents that act with or after surface Ig crosslinking to promote progression to DNA-synthesis or antibody secretion. These experiments should distinguish patients with defective differentiation from patients with defective proliferation. A potentially important new approach is to analyze how cytochalasins, which prevent actin assembly into microfilaments, promote advancement to DNA synthesis, and whether they can do so in patients whose normal mechanisms are blocked. Finally, using a variety of assays for early biochemical and cell surface events in activation, we will discover whether the differentiation factor interferon beta 2, the high and low molecular weight B cell growth factors, and anti-CDw40, utilize any of the known signal transduction pathways or stimulate intermediate events, so we can also determine how far their signals progress in defective B cells. This approach has the dual objective of elucidating normal B cell differentiation and proliferation signals at the biochemical level, and also understanding the physiology of the defective B cells, eventually leading to new strategies for regulation of antibody production.