SIGNAL TRANSDUCTION BY IGM IN B LYMPHOCYTES

免疫球蛋白是负责以下功能的B细胞抗原受体 检测外来抗原并引发一系列事件 结果是产生特异性抗体。 尽管中心作用， 受体免疫球蛋白在产生免疫反应，很少是 我们对这种受体产生信号的机制还不了解。 细胞信号转导机制的研究进展 免疫球蛋白受体受到两个重要特征的阻碍， 这个受体。 首先，受体的胞质内结构域是 由三种氨基酸组成，没有提供关于 受体功能的机制。 理解的第二个障碍 受体免疫球蛋白是，它们与其他几个 在一个实施方案中，多肽在细胞表面上形成多亚基结构。 两 在这些受体相关多肽中，MB-1和B29已被 参与受体组装和细胞表面转运，此外， MB-1和B29在受体交联时迅速磷酸化， 但IgM相关蛋白的功能作用尚不清楚。 我们最近成功地重组了受体免疫球蛋白 通过将克隆的受体成分转移到T细胞中发挥作用， 虽然这些实验已经确定了功能性巨噬细胞， 免疫球蛋白抗原受体的生产要求 对于异源细胞，它们不直接解决抗原的问题， B细胞中受体功能。 拟议研究的长期目标是阐明 膜锚定信号转导的分子要求 B淋巴细胞中免疫球蛋白。 目前的假设是，B29和 MB 1参与B细胞的信号转导， T和B细胞的信号装置在结构上是同源的。 该项目的第一部分将是建立B细胞系， 表达转染的免疫球蛋白受体。 为了这个目的。我们将 使用缺乏几种受体成分的B细胞系。 在项目的第二部分，我们将研究结构特征 产生增加的酪氨酸磷酸化所需的MB 1和B29， 钙动员、肌醇周转和IL-2分泌 受体交联 这些研究对以下方面有潜在的影响： 了解抗原刺激如何触发 体液免疫

Immunoglobulin is the B cell antigen receptor that is responsible for detecting foreign antigens and triggering a cascade of events whose end result is specific antibody production. Despite the central role of receptor immunoglobulin in the generation of immune responses, little is known about the mechanism by which this receptor produces a signal. Progress in understanding the mechanism of signaling by the immunoglobulin receptor has been hindered by two important features of this receptor. First the intracytoplasmic domain of the receptor is composed of three amino acids that offer no specific clues about the mechanism of receptor function. The second impediment to understanding receptor immunoglobulins is that they are associated with several other polypeptides on the cell surface to form a multi-subunit structure. Two of these receptor associated polypeptides MB-1, and B29 have been implicated in receptor assembly and cell surface transport, In addition, both MB-1 and B29 are rapidly phosphorylated upon receptor crosslinking, but the functional role of the IgM-associated proteins is poorly defined. We have recently succeeded in reconstituting receptor immunoglobulin function by transfecting cloned receptor components into T cells and macrophages, Although these experiments have defined the functional requirements for the production of an immunoglobulin antigen receptor in heterologous cells, they do not directly address the problem of antigen receptor function in B cells. The long range goal of the proposed research is to elucidate the molecular requirements for signal transduction by membrane anchored immunoglobulin in B lymphocytes. The working hypothesis is that B29, and MB1 are involved in signal transduction in B cells, and that the signaling apparatus of T and B cells is structurally homologous. The first part of the project will be to establish B cell lines that express transfected immunoglobulin receptors. For this purpose. we will use B cell lines that lack several receptor components. In the second part of the project we will examine the structural features of MB1 and B29 required to produce increased tyrosine phosphorylation, calcium mobilization, inositol turnover and IL-2 secretion in response to receptor crosslinking. These studies have potential implications for understanding how an antigenic stimulus triggers the generation of humoral immunity.