Biased use of VH5 IgE-positive B cells in the nasal mucosa in allergic rhinitis
Biased use of VH5 IgE-positive B cells in the nasal mucosa in allergic rhinitis
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DOI：
10.1016/j.jaci.2005.04.032
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发表时间：
2005-08-01
影响因子：
14.2
通讯作者：
Gould, HJ
中科院分区：
文献类型：
--
作者：
Coker, HA;Harries, HE;Gould, HJ
背景资料：过敏性鼻炎患者的鼻粘膜中富含IgE抗体生成B细胞，因为局部类别转换为IgE。表达的IgE V-H基因也经历原位体细胞超突变以产生克隆家族。这些事件背后的抗原驱动力是unknown.Objective：为了研究超抗原在变应性鼻炎中的可能参与，我们比较了变应性鼻炎患者鼻活检标本和血液中表达的IgE重链基因的可变（VH）基因使用和体细胞突变模式，以及相同活检标本和非变应性对照中伊加Vu的使用。我们从13名患者和4名非过敏对照组的鼻活检标本和7名过敏患者的PBMC中提取mRNA。RT-PCR扩增IgE和伊加VH区，并与对照组的DNA序列进行比较。我们构建了一个V（H）5的分子模型来定位感兴趣的氨基酸。结果：我们观察到与正常PBMC库相比，过敏患者鼻粘膜中IgE和伊加V（H）5转录本的频率显著增加。在鼻粘膜中IgE和伊加V（H）5序列内，置换氨基酸的分布偏向于免疫球蛋白框架区。在V（H）5序列中鉴定的4个非内在突变热点中的3个在框架区1中。热点和保守的V（H）5特异性框架残基在V（H）5表面上形成紧密簇。结论：变应性鼻炎患者鼻粘膜中存在超抗原活性。
Background: IgE antibody-producing B cells are enriched in the nasal mucosa in patients with allergic rhinitis because of local class switching to IgE. The expressed IgE V-H genes also undergo somatic hypermutation in situ to generate clonal families. The antigenic driving force behind these events is unknown.Objective: To examine the possible involvement of a superantigen in allergic rhinitis, we compared the variable (VH) gene use and patterns of somatic mutation in the expressed IgE heavy-chain genes in nasal biopsy specimens and blood from allergic patients and the IgA Vu use in the same biopsy specimens and also those from nonallergic controls.Methods: We extracted mRNA from the nasal biopsy specimens of 13 patients and 4 nonallergic control subjects and PBMCs from 7 allergic patients. IgE and IgA VH regions were RT-PCR amplified, and the DNA sequences were compared with those of control subjects. We constructed a molecular model of V(H)5 to locate amino acids of interest.Results: We observed a significantly increased frequency of IgE and IgA V(H)5 transcripts in the nasal mucosa of the allergic patients compared with the normal PBMC repertoire. Within IgE and IgA V(H)5 sequences in the nasal mucosa, the distribution of replacement amino acids was skewed toward the immunoglobulin framework regions. Three of 4 nonintrinsic hotspots of mutation identified in the V(H)5 sequences were in framework region 1. The hotspots and a conserved V(H)5-specific framework residue form a tight cluster on the surface of V(H)5. Conclusion: Our results provide evidence for the activity of a superantigen in the nasal mucosa in patients with allergic rhinitis.