STRUCTURE/FUNCTION HUMAN B CELL DIFFERENTIATION ANTIGENS

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。

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.