FUNCTION AND EXPRESSION OF LYB-2/CD72

描述（改编自研究者摘要）：主要目的 该项目旨在了解B细胞表面蛋白CD72在 调节B细胞发育和反应性。这些研究将使 广泛使用CD72缺陷突变小鼠，其具有高反应性B细胞 以及B细胞发育和选择的缺陷。第一个目标是进一步 定义CD72调节反应性和发育的机制， CD72和其他表面蛋白之间的功能相互作用的检查 和信号分子。这些研究将利用一些其他 缺乏蛋白质的突变小鼠品系（例如，CD 19、CD 22、林恩），这些细胞似乎 具有与CD72相似或相反的功能， 直接或间接地与CD72信号传导有关。CD72信号传导将在 这样的突变小鼠CD72缺陷对涉及这些信号传导的影响 还将评估其它调节蛋白。CD72双缺陷小鼠 这些其他蛋白质将被产生，并检查它们的表型， 进一步阐明CD72与其他阴性或阳性细胞之间的相互作用， 调节B细胞反应性。第二个目标是确定 CD72胞质尾区特异性基序调控B细胞成熟 和响应能力。这将通过产生表达CD72的小鼠来完成， 哪些特定的氨基酸被认为与信号有关， 变异了将对所得到的小鼠进行表征， 存在于CD72缺陷小鼠中的细胞仍然存在或恢复正常， 这些新的变种人第三个目标是研究缺乏知识的机制， 使用CD72缺陷型小鼠改变耐受性，所述小鼠是转基因的。 特异性B细胞受体（BCR），并且表达或不表达 由BCR识别特异性抗原。最终目的是确定如何 CD 72与脑信号蛋白CD 100相互作用调节B细胞 使用小鼠模型系统过度表达或 缺乏这些蛋白质。这些研究将对 了解调节B细胞发育、耐受性和 自身免疫

DESCRIPTION (adapted from investigator's abstract): The main goal of this project is to understand the role of the B cell surface protein CD72 in the regulation of B cell development and responsiveness. These studies will make extensive use of CD72-deficient mutant mice, which have hyperresponsive B cells and defects in B cell development and selection. The first aim is to further define the mechanisms by which CD72 regulates responsiveness and development by examination of functional interactions between CD72 and other surface proteins and signaling molecules. These studies will take advantage of a number of other mutant mouse strains lacking proteins (e.g., CD 19, CD22, Lyn) that appear to have similar or opposing functions to those of CD72 and that may interact directly or indirectly with CD72 signaling. CD72 signaling will be examined in such mutant mice. The effects of CD72 deficiency upon signaling involving these other regulatory proteins will also be assessed. Mice doubly deficient for CD72 and these other proteins will be generated and their phenotype examined to further elucidate the interactions between CD72 and other negative or positive regulators of B cell responsiveness. The second aim is to define the role of specific motifs in the CD72 cytoplasmic tail in regulating B cell maturation and responsiveness. This will be done by generation of mice expressing CD72 in which particular amino acids thought to be involved in signaling have been mutated. The resultant mice will be characterized to see which of the defects present in CD72-deficient mice are still present or are restored to normal in these new mutants. The third aim is to study the mechanism(s) by which lack of CD72 alters tolerance using CD72-deficient mice that are transgenic for a specific B cell receptor (BCR) and either express or do not express the specific antigen recognized by that BCR. The final aim is to determine how interactions between CD72 and the semaphorin protein CD 100 regulate B cell responsiveness and development using mouse model systems overexpressing or lacking each of these proteins. These studies will be important for understanding the mechanisms regulating B cell development, tolerance and autoimmunity.