SIGNAL TRANSDUCTION BY IGM IN B LYMPHOCYTES

描述(改编自研究人员摘要)：B细胞抗原 受体(BCR)调节许多不同的重要生理过程 在抗体系统中。这些生理反应可以分为两种 类别，不依赖于抗原的类别和诱导的类别 通过抗原。在这笔赠款的第一个资助期内，我们定义了 MIgM和IGA-IGB信号转导之间的基本相互作用。 这一信息随后被用来表明抗原非依赖性事件 包括由膜调节几个不同的转换 免疫球蛋白(MIgm)通过免疫球蛋白-免疫球蛋白信号转导。尽管它 了解与抗原结合是如何使mIgM交联并激活的 IgA-Igb信号转导，mIgM的分子机制 被触发以诱导抗原非依赖性事件的机制仍有待阐明。 在了解抗原非依赖性事件如何被激活方面取得了进展 由于缺乏对交联剂性质的了解而受到阻碍， 可识别的BCR的结构特征，以及是否 新生的mIgM需要在细胞表面表达才能触发这些 回应。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审查结构 B细胞发育所需免疫球蛋白和免疫球蛋白的特性及B细胞应答 与抗原有关。该项目的第二部分将尝试确定 发育中B细胞对mIgM信号的细胞和分子需求 细胞。该项目的第三部分旨在尝试定义 MIgM表达与等位基因排斥的关系这些研究 对了解B细胞是如何发育和 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.