SIGNAL TRANSDUCTION BY IGM IN B LYMPHOCYTES

描述（改编自研究者摘要）：B细胞抗原 受体（BCR）调节许多不同的生理重要过程 在抗体系统中。 这些生理反应可以分为两种 类别，那些是抗原独立的和那些是诱导的 抗原。 在第一个资助期内，我们确定了 mIgM和Iga-Igb信号转导之间的重要相互作用。 然后使用该信息来表明抗原独立事件 包括由膜调节几种不同的转变 免疫球蛋白（mIgm）通过Iga-Igb信号转导。 虽然 理解了与抗原的结合如何交联mIgM并激活 Iga-Igb信号转导子，mIgM通过其分子机制， 触发以诱导抗原非依赖性事件仍有待阐明。 在了解抗原非依赖性事件如何被激活方面的进展， 由于缺乏对交联剂性质的理解而受到阻碍， 所识别的BCR的结构特征，以及 新生mIgM需要在细胞表面表达，以触发这些 应答 拟议研究的长期目标是阐明 激活等位基因排斥和前B细胞的分子机制 过渡 该项目的第一部分将检查结构 B细胞发育和B细胞应答所需的伊加和IgB的特征 抗原。 该项目的第二部分将试图确定 B发育中mIgM信号传导的细胞和分子要求 细胞 项目的第三部分将试图定义 mIgM表达与等位基因排斥的关系。 这些研究 对理解B细胞如何发育和 在体内产生免疫反应。

DESCRIPTION (Adapted from Investigator's abstract): B cell antigen receptors (BCR) regulate many different physiologically important processes in the antibody system. These physiologic responses can be divided into two categories, those which are antigen independent and those which are induced by antigen. During the first funding period for this grant we have defined essential interactions between mIgM and the Iga-Igb signal transducers. This information was then used to show that the antigen independent events include several distinct transitions that are regulated by membrane immunoglobulin (mIgm) through the Iga-Igb signal transducers. Although it is understood how binding to antigen might crosslink mIgM and activate Iga-Igb signal transducers, the molecular mechanisms by which mIgM is triggered to induce antigen independent events remain to be elucidated. Progress in understanding how antigen independent events are activated has been hindered by a lack of understanding of the nature of the crosslinker, the structural features of the BCR that are recognized, and whether the nascent mIgM needs to be expressed on the cell surface to trigger these responses. The long range goal of the proposed research is to elucidate the molecular mechanisms that activate allelic exclusion and the pre-B cell transition. The first part of the project will examine the structural features of Iga and Igb required for B cell development and B cell responses to antigen. The second part of the project will be to try to determine the cellular and molecular requirements for mIgM signaling in developing B cells. The third part of the project will aim to try to define the relationship between mIgM expression and allelic exclusion. These studies have potential implications for understanding how B cells develop and produce immune responses in vivo.