Tissue-specific expression of the low-affinity IgG receptor, FcγRIIb, on human Mast cells
Tissue-specific expression of the low-affinity IgG receptor, FcγRIIb, on human Mast cells
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DOI：
10.3389/fimmu.2018.01244
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发表时间：
2018-06-06
影响因子：
7.3
通讯作者：
Oettgen, Hans C.
中科院分区：
文献类型：
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作者：
Burton, Oliver T.;Epp, Alexandra;Oettgen, Hans C.
速发型超敏反应由过敏原与通过FceRI结合至肥大细胞和嗜碱性粒细胞的特异性IgE抗体的相互作用诱导。虽然需要这些特异性IgE抗体来触发这种反应，但并非所有携带IgE的个体都表现出过敏症状。在一些受试者中观察到的反应性缺乏与相同特异性的IgG抗体的存在相关。在细胞培养研究和食物变态反应和过敏反应的体内动物模型中，已显示此类IgG抗体通过Fc γ RIIb发挥抑制作用。然而，据报道，这种抑制性受体的情况下，从人皮肤来源的原代肥大细胞提出了问题的IgG介导的抑制速发型超敏反应在人类受试者的作用。在这里，我们测试了肥大细胞Fc.RIIb表达可能是组织特异性的假设。利用流式细胞术、定量PCR和来自人源化小鼠组织、人皮肤或人组织的固定石蜡包埋切片中的肥大细胞的免疫荧光染色的组合，我们证实Fc.RIIb不存在于真皮肥大细胞中，但由整个胃肠道的肥大细胞表达。IgE诱导的人源化小鼠全身过敏反应被抗原特异性IgG强烈抑制。这些发现支持IgG通过Fc.RIIb信号传导在抑制超敏反应中发挥生理作用的概念。
Immediate hypersensitivity reactions are induced by the interaction of allergens with specific IgE antibodies bound via FceRI to mast cells and basophils. While these specific IgE antibodies are needed to trigger such reactions, not all individuals harboring IgE exhibit symptoms of allergy. The lack of responsiveness seen in some subjects correlates with the presence of IgG antibodies of the same specificity. In cell culture studies and in vivo animal models of food allergy and anaphylaxis such IgG antibodies have been shown to exert suppression via Fc gamma RIIb. However, the reported absence of this inhibitory receptor on primary mast cells derived from human skin has raised questions about the role of IgG-mediated inhibition of immediate hypersensitivity in human subjects. Here, we tested the hypothesis that mast cell Fc.RIIb expression might be tissue specific. Utilizing a combination of flow cytometry, quantitative PCR, and immunofluorescence staining of mast cells derived from the tissues of humanized mice, human skin, or in fixed paraffin-embedded sections of human tissues, we confirm that Fc.RIIb is absent from dermal mast cells but is expressed by mast cells throughout the gastrointestinal tract. IgE-induced systemic anaphylaxis in humanized mice is strongly inhibited by antigen-specific IgG. These findings support the concept that IgG, signaling via Fc.RIIb, plays a physiological role in suppressing hypersensitivity reactions.