FUNCTION AND EXPRESSION OF LYB-2/CD72

描述（改编自研究者的摘要）：本研究的主要目标 该项目旨在了解 B 细胞表面蛋白 CD72 在 B 细胞发育和反应性的调节。这些研究将使 广泛使用具有高反应性 B 细胞的 CD72 缺陷突变小鼠 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 检查 CD72 和其他表面蛋白之间的功能相互作用 和信号分子。这些研究将利用许多其他 缺乏蛋白质（例如 CD 19、CD22、Lyn）的突变小鼠品系似乎 与 CD72 具有相似或相反的功能，并且可能相互作用 直接或间接地与CD72信号传导。 CD72 信号传导将在 这样的突变小鼠。 CD72 缺陷对涉及这些信号的影响 其他调节蛋白也将被评估。 CD72双重缺陷的小鼠 这些其他蛋白质将被生成并检查它们的表型 进一步阐明CD72与其他阴性或阳性之间的相互作用 B 细胞反应性的调节因子。第二个目标是定义 CD72 胞质尾部的特定基序调节 B 细胞成熟 和反应能力。这将通过产生表达 CD72 的小鼠来完成 哪些特定氨基酸被认为与信号传导有关 变异了。由此产生的小鼠将被表征以查看哪些缺陷 存在于 CD72 缺陷小鼠中的病毒在小鼠中仍然存在或恢复正常 这些新的突变体。第三个目标是研究缺乏 使用 CD72 缺陷转基因小鼠来改变 CD72 的耐受性 特异性 B 细胞受体 (BCR)，表达或不表达 该 BCR 识别的特定抗原。最终目标是确定如何 CD72 和信号蛋白 CD 100 之间的相互作用调节 B 细胞 使用过度表达或的小鼠模型系统进行反应和发育 缺乏这些蛋白质中的每一种。这些研究对于 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.