FUNCTIONAL DIFFERENTIATION IN B LYMPHOCYTES

B 淋巴细胞的功能分化

• 批准号: 6372971
• 负责人: MARVIN B RITTENBERG
• 金额: $ 34.24万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-07-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6372971
• 关键词: Ascaris; B lymphocyte; Proteus; Streptococcus pneumoniae; Trichinella; antibody formation; antibody specificity; antigen antibody reaction; apoptosis; biological signal transduction; cell differentiation; circular dichroism; gene mutation; immunoglobulin genes; laboratory mouse; molecular chaperones; phosphorylcholine; polymerase chain reaction; proteolysis; secretion; transfection

DESCRIPTION (Adapted from the Investigator's abstract): The ability of somatic mutation to modify the course of a humoral immune response is well documented. However, the focus has been almost exclusively on the ability of this process to improve the functional characteristics of representative antibodies; the harmful effects have not been well characterized. Yet in terms of cell numbers, all evidence suggests that B-cell wastage caused by harmful somatic mutations probably far exceeds the number of cells whose antibodies are improved through mutation. The purpose of this project is to gain quantitative insight into the contribution of mutation to B-cell wastage and secondly to exploit the well-known power of harmful mutations, to illuminate function. The investigators have previously made and characterized in vitro the binding of a large number of mutants of the T15 antibody to the hapten, phosphocholine (PC). The hypothesis is that mutant Abs displaying defective Ag binding or secretion in vitro would lead to apoptosis and B-cell wastage if they were to occur in vivo. This hypothesis will be tested in three ways: 1) by examining the ability of mutant antibodies to recognize PC which is displayed in different structural contexts on the surfaces of the pathogenic organisms, Streptococcus pneumoniae, Ascaris suum and Trichinella spiralis as well as Proteus morganii; 2) by testing the ability of mutant antibodies to transmit antigen-induced signals to transfected B lymphoma cells, and 3) by examining apoptotic GC B-cells for mutations in the VH1 gene of T15 shown to be harmful in vitro. These studies bear on B-cell wastage and homeostasis and the causes of apoptosis in germinal centers where recent evidence has suggested some lymphoid tumors such as Hodgkin's disease may originate.

描述（根据调查员的摘要改编）： 体细胞突变以修饰体液免疫反应的过程很好 记录。 但是，重点几乎完全放在能力上 这一过程以提高代表性的功能特征 抗体；有害效应尚未得到很好的特征。 但是 细胞数的条款，所有证据表明B细胞浪费是由 有害的体细胞突变可能远远超过了其细胞数量 通过突变改善抗体。 这个项目的目的是 获得对突变对B细胞的贡献的定量见解 浪费，其次是利用众所周知的有害突变的力量， 点亮功能。 调查人员以前做过 体外表征了大量T15突变体的结合 抗触觉，磷胆碱（PC）的抗体。 假设是突变体 在体外表现出缺陷Ag结合或分泌的ABS会导致 如果要在体内发生凋亡和B细胞浪费。 这个假设 将通过三种方式进行测试：1）检查突变体的能力 识别以不同结构显示的PC的抗体 致病生物表面上的环境，链球菌 肺炎，阿斯卡里斯·苏姆（Ascaris suum）和毛trichinella spiralis以及proteus Morganii; 2）通过测试突变抗体发射的能力 抗原引起的转染B淋巴瘤细胞的信号，3）检查 在T15的VH1基因中用于突变的凋亡GC B细胞显示为 体外有害。 这些研究对B细胞浪费和稳态以及 最近有证据的生发中心凋亡的原因 建议一些淋巴样肿瘤（例如霍奇金氏病）可能起源。