ACTIVATION EVENTS IN TOLERANT AND NORMAL B CELLS

患有自身免疫病的患者产生过多的某些抗体，尤其是 那些指向“自我”的。我们目前针对这些疾病的原始治疗方法 如果我们理解并能够操纵 B淋巴细胞活化的早期事件足以抑制特异性 恢复自我耐受性的免疫反应。取得的主要成就 在过去的十年里，细胞免疫学一直在理解 抗体反应受多种生长和分化调节 T细胞和巨噬细胞的因子(淋巴因子)，并定义几个 不同的耐受机制。其中一种机制是内在的 B细胞的耐受性来系统地解决这个问题。我们有 选定了六个此类事件，包括重大早期、中期和 晚期事件：1)膜去极化(1小时内)；2)细胞增多 体积(不到1天)；3)细胞表面Ia表达增加(在 约1天)；4)表面Ig加速脱落；5)加速 第1天至第4天表面免疫球蛋白M和免疫球蛋白的替换；以及6)进展 通过细胞周期进入S期，在第3天到第4天。我们会显示 这些事件可以在纯化的抗原结合细胞中引发， 耐受性动物和非耐受性动物通过以下形式的“信号1”： 抗Mu、抗伽玛、脂多糖、葡聚糖硫酸盐和胸腺非依赖性 从属抗原。然后我们将展示这些早期的表现 事件受添加的“第二信号”的影响 白介素1、B细胞生长因子1或2、两种T细胞替代因子 不同的T细胞株和干扰素。因此，我们的研究具有两面性 揭示淋巴因子和内在耐受对人类免疫功能的影响 反应的B细胞的生理学。

Patients with autoimmunity make too much of certain antibodies, especially those directed to "self". Our crude current therapies for these conditions could be greatly improved if we only understood and could manipulate the early events in B lymphocyte activation well enough to turn down specific immune responses to restore self-tolerance. Major accomplishments of cellular immunology in the last decade have been to understand how the antibody response is regulated by a variety of growth and differentiation factors (lymphokines) from T cells and macrophages, and to define several different mechanisms of tolerance. One of those mechanisms is intrinsic tolerance in B cells to attack this problem systematically. We have selected six such events, including significant early, intermediate and late events: 1) membrane depolarization (within 1 hr); 2) increase in cell volume (in less than 1 day); 3) increase in cell surface Ia expression (at about 1 day); 4) accelerated shedding of surface Ig; 5) accelerated replacement of surface IgM and IgG from day 1 to day 4; and 6) progress through the cell cycle to S phase on day 3 to 4. We will show whether these events can be elicited in purified antigen-binding cells from tolerant and nontolerant animals by the following forms of "signal 1": anti-Mu, anti-Gamma, LPS, dextran sulfate, and thymus-independent and dependent antigen. Then we will show how the performance of these early events is affected by the addition of a "second signal" in the form of interleukin 1, B cell growth factors 1 or 2, two T replacing factors from different T cell lines, and interferon. Thus our research has the dual purpose of revealing the impact of lymphokines and intrinsic tolerance on the physiology of the responding B cell.