GROWTH/DIFFERENTIATION FACTORS IN NORMAL/IMMUNE B CELLS

常见变异患者的B细胞 泛低丙种球蛋白血症本质上不能成熟， 高速率抗体分泌细胞在正常的步伐，即使在 存在正常相互作用的T细胞和单核细胞。 然而，在这方面， 他们能够在早期和中期 激活事件正常，因此无法激活 似乎不是他们的问题。 预计识别 不同患者的B细胞中的缺陷步骤将揭示 关于正常的B细胞激活，我们建议最近利用 描述了用因子激活B细胞的替代模式，或 与表面Ig交联一起或在表面IG交联之后起作用以促进 发展为DNA合成或抗体分泌。 这些 实验应该区分有缺陷的患者 与有缺陷的增殖患者的分化。 一 一种潜在的重要新方法是分析 细胞松弛素，阻止肌动蛋白组装成微丝， 促进DNA合成的进展，以及它们是否能 正常机制受阻的患者也是如此。 最后， 使用多种测定早期生物化学和细胞表面 在激活事件中，我们将发现 因子干扰素β 2，高和低分子量B细胞 生长因子和抗CDw40，利用任何已知的信号 转导途径或刺激中间事件，所以我们 还可以确定它们的信号在有缺陷的B中的进展程度 细胞 这种方法具有双重目标，即阐明正常的 B细胞分化和增殖的生化信号 水平，并了解生理缺陷的B 细胞，最终导致新的策略， 抗体生产。

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.