STRUCTURE/FUNCTION HUMAN B CELL DIFFERENTIATION ANTIGENS

这项提议的基本目标是研究人类B细胞如何 激活和生长是通过细胞表面分子来调节的。我们 将专注于表征配体和信号转导途径 由三种主要的B细胞相关表面分子，即CD20诱导， CD40和Bgp95。我们将利用一套激动型的单抗 针对这些标记的抗体(MAb)和表达的全长cDNA 编码CD20和CD40的载体。我们的具体目标是：目标1)定义 CD20和CD40的配体，利用转化的细胞系 CD20或CD40；目的2)表征信号转导 通过测量肌醇磷脂代谢来调节CD20和CD40的途径 蛋白激酶和/或抗CD40；目的3)分离编码Bgp95的cDNA 用于表征该表面的结构和功能 参与调节B细胞激活的分子；以及目的4) 评估膜蛋白酪氨酸磷酸酶(PTPase)的作用 CD45在调节能力(CD20、Bgp95)和进程(CD40)中的作用 人类B细胞中的信号。这些研究不仅有助于阐明 调节小静息B细胞的基本机制，但也会 提供有关如何从G0过渡到G1阶段的新信息 细胞周期受到控制。

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.