Takhar Pooja, Corrigan Christopher J, Smurthwaite Lyn, O'Connor Brian J, Durham Stephen R, Lee Tak H, Gould Hannah J
Randall Division of Cell and Molecular Biophysics, King's College London, UK.
J Allergy Clin Immunol. 2007 Jan;119(1):213-8. doi: 10.1016/j.jaci.2006.09.045.
Class switching from IgM/IgG/IgA to IgE is required for B cells to express IgE. This requires class switch recombination in the Ig heavy-chain gene locus. It is generally believed that class switch recombination occurs in lymphoid tissue, but it was recently shown that class switching to IgE occurs in the nasal mucosa in allergic rhinitis.
We aimed to determine whether class switching to IgE also occurs in the bronchial mucosa in asthma, and to look for possible differences/similarities between atopic and nonatopic asthma.
We have used RT-PCR to examine epsilon immunoglobulin heavy-chain germline gene transcripts (GLTs; epsilonGLTs), epsilon circle transcripts (CTs; Ivarepsilon-Cmu CT or Ivarepsilon-Cgamma CT), and mRNA encoding the heavy chain of IgE (epsilon mRNA) and activation-induced cytidine deaminase (AID) in bronchial biopsies from atopic patients with asthma, nonatopic patients with asthma, atopic controls without asthma, and nonatopic controls without asthma (10 subjects in each group).
The varepsilonGLT and AID mRNA were detectable in the bronchial mucosa of subjects in all 4 groups. In contrast, Iepsilon-Cmu CT, Ivarepsilon-Cgamma CT, and epsilon mRNA were detectable in the bronchial mucosa of the majority of both atopic and nonatopic patients with asthma, but rarely in the controls without asthma.
The bronchial mucosa is a site primed in all individuals for class switching to IgE, because of B-cell expression of epsilonGLT and AID mRNA. However, it is only in patients with asthma, regardless of atopic status, that class switching to IgE occurs.
Our findings reveal prospects for local targeting of the Ig class switch mechanism in the management of atopic and nonatopic asthma.
B细胞表达IgE需要从IgM/IgG/IgA类别转换为IgE。这需要在Ig重链基因座中进行类别转换重组。一般认为类别转换重组发生在淋巴组织中，但最近研究表明，过敏性鼻炎中向IgE的类别转换发生在鼻黏膜中。
我们旨在确定哮喘患者的支气管黏膜中是否也会发生向IgE的类别转换，并寻找特应性哮喘和非特应性哮喘之间可能存在的差异/相似之处。
我们使用逆转录聚合酶链反应（RT-PCR）检测了来自特应性哮喘患者、非特应性哮喘患者、无哮喘的特应性对照者和无哮喘的非特应性对照者（每组10名受试者）支气管活检样本中的ε免疫球蛋白重链种系基因转录本（GLTs；εGLTs）、ε环转录本（CTs；Iε-Cμ CT或Iε-Cγ CT）、编码IgE重链的mRNA（ε mRNA）以及活化诱导胞苷脱氨酶（AID）。
所有4组受试者的支气管黏膜中均可检测到εGLT和AID mRNA。相比之下，大多数特应性和非特应性哮喘患者的支气管黏膜中可检测到Iε-Cμ CT、Iε-Cγ CT和ε mRNA，但无哮喘的对照者中很少能检测到。
由于B细胞表达εGLT和AID mRNA，支气管黏膜是所有个体中准备好向IgE类别转换的位点。然而，只有哮喘患者，无论是否为特应性，才会发生向IgE的类别转换。
我们的研究结果揭示了在特应性和非特应性哮喘管理中对Ig类别转换机制进行局部靶向治疗的前景。
