Lichtenstein L M, Kagey-Sobotka A, White J M, Hamilton R G
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224.
J Immunol. 1992 Jun 15;148(12):3929-36.
We have reexamined the ability of anti-human IgG antibodies to induce histamine release from human basophils. A panel of purified murine mAbs with International Union of Immunological Societies-documented specificity for each of the four subclasses of human IgG was used. Of the 24 allergic subjects studied, the basophils of 75% (18/24) released greater than 10% histamine to one or more anti-IgG1-4 mAb, whereas none of the 13 nonatopic donor's basophils released histamine after stimulation with optimal amounts of anti-IgG mAb. The basophils of 85% (11/13) of the nonatopic donors did respond to anti-IgE challenge, as did 92% (22/24) of the atopic donor cells. Histamine release was induced most frequently by anti-IgG3, and 10/18 anti-IgG responder cells released histamine with mAb specific for two or more different subclass specificities. The rank order for induction of histamine release was anti-IgG3 greater than anti-IgG2 greater than IgG1 greater than anti-IgG4. As in our previous study using polyclonal anti-IgG, 100- to 300-micrograms/ml quantities of the anti-IgG mAb were required for maximal histamine release, about 1000-fold higher than those for comparable release with anti-human IgE. Specificity studies using both immunoassays and inhibition studies with IgE myeloma protein indicated that anti-IgG induced histamine release was not caused by cross-reactivity with IgE. Ig receptors were opened by lactic acid treatment so that the cells could be passively sensitized. Neither IgE myeloma nor IgG myeloma (up to 15 mg/ml) proteins could restore the response to anti-IgG mAb. However, sera from individuals with leukocytes that released histamine upon challenge with anti-IgG mAb could passively sensitize acid-treated leukocytes from both anti-IgG responder and nonresponder donors for an anti-IgG response. The only anti-IgG mAb that induced release from these passively sensitized cells were those to which the serum donor was responsive. Sera from non-IgG responders could not restore an anti-IgG response. These data led to the hypothesis that the IgG specific mAb were binding to IgG-IgE complexes that were attached to the basophil through IgE bound to the IgE receptor. This was shown to be correct because passive sensitization to anti-IgG could be blocked by previous exposure of the basophils to IgE. We conclude that anti-IgG-induced release occurs as a result of binding to IgG anti-IgE antibodies and cross-linking of the IgE receptors on basophils.
我们重新研究了抗人IgG抗体诱导人嗜碱性粒细胞释放组胺的能力。使用了一组经国际免疫学会鉴定对人IgG四个亚类具有特异性的纯化鼠单克隆抗体。在研究的24名过敏受试者中，75%（18/24）的嗜碱性粒细胞对一种或多种抗IgG1 - 4单克隆抗体释放超过10%的组胺，而13名非特应性供者的嗜碱性粒细胞在用最佳量的抗IgG单克隆抗体刺激后均未释放组胺。85%（11/13）的非特应性供者的嗜碱性粒细胞对抗IgE刺激有反应，92%（22/24）的特应性供者细胞也有反应。抗IgG3诱导组胺释放最为常见，18名抗IgG反应细胞中有10个对两种或更多不同亚类特异性的单克隆抗体释放组胺。诱导组胺释放的顺序为抗IgG3＞抗IgG2＞抗IgG1＞抗IgG4。正如我们之前使用多克隆抗IgG的研究一样，最大组胺释放需要100 - 300微克/毫升的抗IgG单克隆抗体，这比用抗人IgE进行类似释放所需的量高约1000倍。使用免疫测定和IgE骨髓瘤蛋白抑制研究的特异性研究表明，抗IgG诱导的组胺释放不是由与IgE的交叉反应引起的。用乳酸处理打开Ig受体，使细胞能够被动致敏。IgE骨髓瘤蛋白和IgG骨髓瘤蛋白（高达15毫克/毫升）均不能恢复对抗IgG单克隆抗体的反应。然而，用抗IgG单克隆抗体刺激后白细胞释放组胺的个体的血清可以使抗IgG反应者和非反应者供者的酸处理白细胞被动致敏以产生抗IgG反应。唯一能从这些被动致敏细胞诱导释放的抗IgG单克隆抗体是血清供者有反应的那些。非IgG反应者的血清不能恢复抗IgG反应。这些数据导致这样的假设，即IgG特异性单克隆抗体与通过结合到IgE受体上的IgE附着于嗜碱性粒细胞的IgG - IgE复合物结合。这被证明是正确的，因为嗜碱性粒细胞预先暴露于IgE可阻断对抗IgG的被动致敏。我们得出结论，抗IgG诱导的释放是由于与IgG抗IgE抗体结合并使嗜碱性粒细胞上的IgE受体交联所致。
