Yin L, Schwartzberg P, Scharton-Kersten T M, Staudt L, Lenardo M
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, U.S.A.
Mol Immunol. 1997 Apr;34(6):481-91. doi: 10.1016/s0161-5890(97)00053-9.
Ly-GDI (lymphoid-specific guanosine diphosphate (GDP) dissociation inhibitor), also called D4-GDI, is preferentially expressed in hematopoietic tissues including bone marrow, thymus, spleen and lymph nodes. It binds to the small guanosine triphosphate (GTP)-binding protein Rho and inhibits GDP dissociation from Rho proteins. To explore the function of Ly-GDI in lymphocytes, we have generated Ly-GDI-deficient mice by gene targeting. These mice showed no striking abnormalities of lymphoid development or thymocyte selection. The mice also exhibited, for the most part, normal immune responses including lymphocyte proliferation, IL-2 production, cytotoxic T lymphocyte activity, antibody production, antigen processing and presentation, immune cell aggregation and migration, and protection against an intracellular protozoan. However, Ly-GDI-deficient mice exhibited deregulated T and B cell interactions after in vitro cultivation of mixed lymphocyte populations in concanavalin A (Con A) leading to overexpansion of B lymphocytes. Further studies revealed that Ly-GDI deficiency decreased IL-2 withdrawal apoptosis of lymph node cells while dexamethasone- and T cell receptor-induced apoptosis remained intact. These data implicate the regulation of the Rho GTPase by Ly-GDI in lymphocyte survival and responsiveness, but suggest that these functions may be partially complemented by other Rho regulatory proteins when the Ly-GDI protein is deficient.
淋巴细胞特异性鸟苷二磷酸（GDP）解离抑制剂（Ly-GDI），也称为D4-GDI，在包括骨髓、胸腺、脾脏和淋巴结在内的造血组织中优先表达。它与小的鸟苷三磷酸（GTP）结合蛋白Rho结合，并抑制GDP从Rho蛋白上解离。为了探究Ly-GDI在淋巴细胞中的功能，我们通过基因靶向技术构建了Ly-GDI缺陷小鼠。这些小鼠在淋巴发育或胸腺细胞选择方面没有明显异常。这些小鼠在很大程度上还表现出正常的免疫反应，包括淋巴细胞增殖、白细胞介素-2产生、细胞毒性T淋巴细胞活性、抗体产生、抗原加工和呈递、免疫细胞聚集和迁移以及对细胞内原生动物的抵抗力。然而，在体外使用伴刀豆球蛋白A（Con A）培养混合淋巴细胞群体后，Ly-GDI缺陷小鼠表现出T细胞和B细胞相互作用失调，导致B淋巴细胞过度增殖。进一步研究表明，Ly-GDI缺陷减少了淋巴结细胞因白细胞介素-2撤除引起的凋亡，而地塞米松和T细胞受体诱导的凋亡则保持完整。这些数据表明Ly-GDI对Rho GTP酶的调节在淋巴细胞存活和反应性中起作用，但也表明当Ly-GDI蛋白缺乏时，这些功能可能部分由其他Rho调节蛋白补充。
