Long term maintenance of IgE-mediated memory in mast cells in the absence of detectable serum IgE
Long term maintenance of IgE-mediated memory in mast cells in the absence of detectable serum IgE
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DOI：
10.4049/jimmunol.170.2.775
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发表时间：
2003-01-15
影响因子：
4.4
通讯作者：
Karasuyama, H
中科院分区：
文献类型：
--
作者：
Kubo, S;Nakayama, T;Karasuyama, H
肥大细胞和嗜碱性细胞参与过敏反应不具有克隆型Ag受体。然而，它们可以通过Ag特异性IgE与表面表达的FcepsilonRI结合获得Ag特异性。先前的研究表明，IgE结合诱导FcepsilonRI在细胞表面的稳定和积累，导致FcERI的上调。在本研究中，我们通过比较血清IgE水平、FcepsilonERI表达和诱导全身过敏反应的动力学，进一步分析了体内肥大细胞和嗜碱性细胞中IgE介导的记忆的维持。单次静脉注射三硝基苯特异性IgE可诱导B细胞缺陷小鼠腹膜肥大细胞上FcepsilonRI表达上调8倍。血清IgE水平在第6天无法检测到，但用抗IgE单抗治疗小鼠在第14、28和42天引起体温显著下降。用三硝基苯-牛血清白蛋白（而非牛血清白蛋白）代替抗ige单抗的结果相似，表明过敏反应的Ag特异性。在IgE被动致敏的正常小鼠中也观察到这种过敏反应中ag特异性反应的长期维持，尽管持续时间比B细胞缺陷小鼠短。具有不同特异性的IgE的出现不会干扰肥大细胞和嗜碱性细胞的IgE介导记忆的维持。这些结果表明，ige介导的FcepsilonRI的稳定和上调使肥大细胞和嗜碱性细胞不仅获得Ag特异性，而且在体内长时间保持记忆。
Mast cells and basophils involved in allergic responses do not have clonotypic Ag receptors. However, they can acquire Ag specificity through binding of Ag-specific IgE to FcepsilonRI expressed on their surface. Previous studies demonstrated that IgE binding induced the stabilization and accumulation of FcepsilonRI on the cell surface and resulted in up-regulation of FcERI. In this study we have further analyzed the maintenance of IgE-mediated memory in mast cells and basophils in vivo by comparing kinetics of serum IgE levels, FcepsilonERI expression, and ability to induce systemic anaphylaxis. A single i.v. injection of trinitrophenyl-specific IgE induced 8-fold up-regulation of FcepsilonRI expression on peritoneal mast cells in B cell-deficient (mum(-/-)) mice. Serum IgE levels became undetectable by day 6, but the treatment of mice with anti-IgE mAb induced a significant drop in body temperature on days 14, 28, and 42. The administration of trinitrophenyl -BSA, but not BSA, in place of anti-IgE mAb gave similar results, indicating the Ag specificity of the allergic response. This long term maintenance of Ag-specific reactivity in the allergic response was also observed in normal mice passively sensitized with IgE even though the duration was shorter than that in B cell-deficient mice. The appearance of IgE with a different specificity did not interfere with the maintenance of IgE-mediated memory of mast cells and basophils. These results suggest that IgE-mediated stabilization and up-regulation of FcepsilonRI enables mast cells and basophils not only to acquire Ag specificity, but also to maintain memory in vivo for lengthy periods of time.