IgG antibodies produced during subcutaneous allergen immunotherapy mediate inhibition of basophil activation via a mechanism involving both FcγRIIA and FcγRIIB
IgG antibodies produced during subcutaneous allergen immunotherapy mediate inhibition of basophil activation via a mechanism involving both FcγRIIA and FcγRIIB
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DOI：
10.1016/j.imlet.2009.12.001
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发表时间：
2010-05-04
影响因子：
4.4
通讯作者：
Cambier, John C.
中科院分区：
文献类型：
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作者：
Cady, Carol T.;Powell, Maree S.;Cambier, John C.
接受皮下变应原免疫疗法（IT）的大多数人类受试者对其变应原的敏感性降低。多种因素可以解释IT的疗效，一些证据支持过敏原特异性IgG抗体的作用。对于这些抗体是通过阻断过敏原与IgE的结合还是通过肥大细胞和嗜碱性粒细胞上的低亲和力IgG受体（Fc γ RIIB）启动活性抑制性信号传导而起作用存在争议。在这项研究中，我们解决了这个问题，使用外周血猫非过敏，猫过敏，免疫治疗猫过敏的主题。接受IT的受试者的血液含有IgG抗体，其通过抑制性IgG受体Fc γ RIIB特异性抗体阻断的机制介导嗜碱性粒细胞活化的抑制。令人惊讶的是，抑制作用也被非糖基化的、puplatin非FcR结合的、对Fc γ RIIA特异的抗体阻断，表明该受体对观察到的作用有贡献。与协同效应一致，发现离体嗜碱性粒细胞表达两种IgG受体。在其他研究中，我们发现来自长期暴露于过敏原并产生猫过敏原特异性IgE和IgG的受试者的嗜碱性粒细胞对过敏原反应迟钝。这些研究证实IT期间产生的IgG抗体主要通过刺激抑制性信号传导起作用，并表明Fc γ RIIA和Fc γ RIIB在激活抑制性信号传导回路中协同发挥作用。我们认为，在正常生理条件下，其中只有一小部分Fc γ RIIA被单一过敏原特异性IgE占据，Fc γ RIIA共聚集可能通过提供活化的林恩来刺激抑制性Fc γ RIIB功能的活化。(C)2009 Elsevier B.V.保留所有权利。
The majority of human subjects who receive subcutaneous allergen immunotherapy (IT) develop decreased sensitivity to their allergens. Multiple factors may explain the efficacy of IT, some evidence support a role for allergen specific IgG antibodies. There is controversy whether such antibodies act by blocking allergen binding to IgE or initiation of active inhibitory signaling through low affinity IgG receptors (Fc gamma RIIB) on mast cells and basophils. In this study, we addressed this question using peripheral blood from cat non-allergic, cat allergic, and immunotherapy-treated cat allergic subjects. Blood from subjects who received IT contain IgG antibodies that mediate inhibition of basophil activation by a mechanism that is blocked by antibodies specific for the inhibitory IgG receptor Fc gamma RIIB. Surprisingly, inhibition was also blocked by aglycosylated, putatively non-FcR binding, antibodies that are specific for the Fc gamma RIIA, suggesting a contribution of this receptor to the observed effect. Consistent with a cooperative effect, ex vivo basophils were found to express both IgG receptors. In other studies we found that basophils from subjects who were both chronically exposed to allergen and were producing both cat allergen specific IgE and IgG, are hyporesponsive to allergen. These studies confirm that IgG antibodies produced during IT act primarily by stimulation of inhibitory signaling, and suggest that Fc gamma RIIA and Fc gamma RIIB function cooperatively in activation of inhibitory signaling circuit. We suggest that under normal physiologic conditions in which only a small proportion of Fc epsilon RI are occupied by IgE of a single allergen specificity, Fc gamma RIIA co-aggregation may, by providing activated Lyn, be required to fuel activation of inhibitory Fc gamma RIIB function. (C) 2009 Elsevier B.V. All rights reserved.