FUNCTION AND EXPRESSION OF LYB-2/CD72

描述(改编自调查人员摘要)：主要目标 该项目旨在了解B细胞表面蛋白CD72在人类免疫缺陷中的作用。 调节B细胞的发育和反应性。这些研究将使 CD72缺陷突变小鼠的广泛应用，这些突变小鼠具有高反应性B细胞 B细胞发育和选择方面的缺陷。第一个目标是进一步 定义CD72通过以下方式调节反应性和发育的机制 CD72与其他表面蛋白功能相互作用的研究 和信号分子。这些研究将利用其他一些 缺乏蛋白质(如CD19、CD22、LYN)的突变小鼠品系 具有与CD72相似或相反的功能，并可能相互作用 直接或间接通过CD72信号转导。将在中检查CD72信令 这样的突变小鼠。CD72缺乏对涉及这些信号转导的影响 其他调节蛋白也将被评估。双缺乏CD72的小鼠 这些其他蛋白质将被产生，并检测其表型以 进一步阐明CD72与其他阴性或阳性的相互作用 B细胞反应性的调节因子。第二个目标是定义 CD72胞浆尾部调控B细胞成熟的特异性基序 和响应性。这将通过一代表达CD72的小鼠在 哪些特定的氨基酸被认为参与了信号转导 变异了。由此产生的小鼠将被表征以查看哪种缺陷 在CD72缺陷小鼠中仍然存在或恢复到正常 这些新的变种人。第三个目的是研究(S)缺乏的机制 CD72转基因小鼠改变耐受性的研究 特异性B细胞受体(BCR)，并且表达或不表达 由该BCR识别特定抗原。最终目标是确定如何 CD72与信号素蛋白CD100相互作用调节B细胞 使用过度表达OR的小鼠模型系统的反应性和发育 缺少所有这些蛋白质。这些研究将对以下方面具有重要意义 了解B细胞发育、耐受和免疫调节机制 自身免疫力。

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.