STRUCTURE/FUNCTION HUMAN B CELL DIFFERENTIATION ANTIGENS

结构/功能人 B 细胞分化抗原

• 批准号: 3293719
• 负责人: Edward A Clark
• 金额: $ 16.94万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-12-01 至 1994-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3293719
• 关键词: B lymphocyte; CD antigens; biological signal transduction; cell cell interaction; cell differentiation; cell growth regulation; cell transformation; laboratory mouse; leukocyte activation /transformation; lipid metabolism; membrane proteins; molecular cloning; monoclonal antibody; phosphatidylinositols; phosphorylation; protein kinase; protein structure function; surface antigens; transfection

The fundamental goal of this proposal is to investigate how human B cell activation and growth are regulated through cell surface molecules. We will focus on characterizing the ligands and signal transduction pathways induced via three major B cell-associated surface molecules, namely CD20, CD40 and Bgp95. We will make use of a set of agonistic monoclonal antibodies (mAb) to these markers and full length cDNAs in expression vectors encoding CD20 and CD40. Our specific aims are: Aim 1) to define the ligands for CD20 and CD40, making use of cell lines transformed with either CD20 or CD40; Aim 2) to characterize the signal transduction pathways for CD20 and CD40 by measuring inositol phospholipid metabolism, protein kinases and/or anti-CD40; Aim 3) to isolate cDNAs encoding Bgp95 for use in characterizing the structure and function of this surface molecule involved in the regulation of B cell activation; and Aim 4) to assess the role that the membrane protein tyrosine phosphatase (PTPase) CD45 plays in regulating competence (CD20, Bgp95) and progression (CD40) signals in human B cells. These studies will help to elucidate not only the basic mechanisms regulating small resting B cells, but will also provide new information on how the transition of G0 to the Gl phase of the cell cycle is controlled.

这项计划的基本目标是研究人类B细胞 活化和生长通过细胞表面分子调节。 我们 将集中于表征配体和信号转导途径 通过三种主要的B细胞相关表面分子，即CD 20， CD 40和Bgp 95。 我们将使用一组激动性单克隆抗体， 这些标记物的抗体（mAb）和表达的全长cDNA 编码CD 20和CD 40的载体。 我们的具体目标是：目标1）定义 CD 20和CD 40的配体，利用用 CD 20或CD 40;目的2）表征信号转导 通过测量肌醇磷脂代谢， 目的3）分离编码Bgp 95的cDNA 用于表征该表面的结构和功能 参与调节B细胞活化的分子;和目的4） 评估膜蛋白酪氨酸磷酸酶（PTP 3） CD 45在调节能力（CD 20，Bgp 95）和进展（CD 40）中发挥作用 人类B细胞的信号。 这些研究不仅有助于阐明 调节小静息B细胞的基本机制，但也将 提供了新的信息，如何过渡的G 0到G1阶段的 细胞周期是可控的。