IgE Transcripts in the Circulation of Allergic Children Reflect a Classical Antigen-Driven B Cell Response and Not a Superantigen-Like Activation
IgE Transcripts in the Circulation of Allergic Children Reflect a Classical Antigen-Driven B Cell Response and Not a Superantigen-Like Activation
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DOI：
10.4049/jimmunol.0902942
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发表时间：
2010-08-15
影响因子：
4.4
通讯作者：
Zemlin, Michael
中科院分区：
文献类型：
--
作者：
Kerzel, Sebastian;Rogosch, Tobias;Zemlin, Michael
过敏性哮喘是儿童期最常见的慢性疾病。尽管IgE是过敏性疾病中的核心效应分子，但IgE反应的本质仍存在争议。我们研究的目的是阐明过敏性儿童循环中的IgE库是代表经典的抗原驱动的寡克隆B细胞反应、B细胞亚群的超抗原样激活，还是多克隆B - 1细胞扩增。我们使用一种高度敏感的逆转录聚合酶链反应（RT - PCR）方法，对13名过敏性哮喘儿童的IgE重链转录本进行扩增、克隆和测序。我们获得了1366个有功能的IgE序列，这是目前人类IgE转录本最广泛的集合。与来自同一批儿童的IgM转录本相比，IgE转录本中的体细胞突变率显著提高（21%对72%；p < 0.001），这使得多克隆B - 1反应不太可能。此外，IgE序列显示出抗原选择显著增强，因此表明是一种具有亲和力成熟的经典抗原驱动的免疫反应（p < 0.001）。与最近的几项研究相反，IgE转录本中重链Ig可变基因片段的使用模式遵循种系复杂性，这反驳了超抗原样相互作用。我们得出结论，过敏性哮喘儿童循环中的IgE转录本反映了一种经典的适应性B - 2细胞反应。这项研究为更好地描述在免疫调节治疗（如抗IgE治疗或过敏原特异性免疫治疗）下的IgE反应提供了参考数据。《免疫学杂志》，2010年，185卷：2253 - 2260页
Allergic asthma is the most frequent chronic disorder in childhood. Although IgE is a central effector molecule in allergic diseases, the nature of the IgE response is still under debate. The objective of our study was to clarify whether the IgE repertoire in the circulation of allergic children represents a classical Ag-driven and oligoclonal B cell response, a superantigen-like activation of a subset of B cells, or a polyclonal B-1 cell expansion. Using a highly sensitive RT-PCR method, we amplified, cloned, and sequenced IgE H chain transcripts from 13 children with allergic asthma. We gained 1366 functional IgE sequences, which currently represent the most extensive collection of human IgE transcripts. Compared to IgM transcripts from the same children, the somatic mutation rate was significantly enhanced in IgE transcripts (21% versus 72%; p < 0.001), which renders a polyclonal B-1 response unlikely. Moreover, IgE sequences displayed significantly enhanced Ag selection and hence were indicative of a classical Ag-driven immune response with affinity maturation (p, 0.001). In contrast to several recent studies, the usage pattern of variable gene segment of the H Ig chain in IgE transcripts followed the germline complexity, arguing against a superantigen-like interaction. We conclude that IgE transcripts in the circulation of children with allergic asthma reflect a classical adaptive B-2 cell response. This study provides reference data for a better characterization of the IgE response under immunomodulating therapies, such as anti-IgE therapy or allergen-specific immunotherapy. The Journal of Immunology, 2010, 185: 2253-2260.