慢性鼻-鼻窦炎伴鼻息肉中局部受体修正和同种型转换至 IgE。

Local receptor revision and class switching to IgE in chronic rhinosinusitis with nasal polyps.

机构信息

Upper Airways Research Laboratory, Department of Otorhinolaryngology, Ghent University, B-9000 Ghent, Belgium.

出版信息

Allergy. 2013 Jan;68(1):55-63. doi: 10.1111/all.12054. Epub 2012 Nov 15.

DOI:10.1111/all.12054

PMID:23157682

Abstract

BACKGROUND

Chronic rhinosinusitis with nasal polyps (NP) and allergic rhinitis (AR) is characterized by local Th2 inflammation and up-regulation of IgE; however, IgE in NP is 'polyclonal' and allergen specific, whereas IgE in AR is 'oligoclonal' and allergen specific. Germinal center (GC) reactions occur in AR, while only the formation of GC-like structures in NP is described. The aim of this study was to investigate the involvement of local IgE production, class switch recombination, and receptor revision in NP.

METHODS

We compared the levels of local IgE, germline gene transcripts, and mature Ig mRNA expression, recombination activating gene (RAG1 and RAG2), key markers of Th2 inflammation, and GC reactions in NP tissue vs AR and control tissue. Nasal mucosa was immunostained for the co-expression of RAG1 and RAG2 in B cells, plasma cells, and T cells, using dual or triple immunofluorescence (IF).

RESULTS

In NP, local IgE level and key markers of local class switching are increased compared with AR and normal controls (NC). In NP, switch circle transcripts reveal ongoing local class switch recombination to IgE. Up to 30% of B cells, plasma cells, and T cells in nasal polyps re-express both RAG1 and RAG2, required for receptor revision. RAG1 and RAG2 mRNA concentrations are increased in NP and correlated with the magnitude of inflammation and the presence of S. aureus enterotoxin (superantigen)-specific IgE in the nasal polyp mucosa.

CONCLUSION

Our results provide the first evidence of local receptor revision and class switching to IgE, and B-cell differentiation into IgE-secreting plasma cells in NP.

摘要

背景

伴有鼻息肉（NP）和过敏性鼻炎（AR）的慢性鼻-鼻窦炎的特征为局部 Th2 炎症和 IgE 上调；然而，NP 中的 IgE 是“多克隆”和变应原特异性的，而 AR 中的 IgE 是“寡克隆”和变应原特异性的。生发中心（GC）反应发生在 AR 中，而 NP 中仅描述了 GC 样结构的形成。本研究旨在探讨 NP 中局部 IgE 产生、类别转换重组和受体修正的参与情况。

方法

我们比较了 NP 组织、AR 组织和对照组织中局部 IgE 水平、胚系基因转录物和成熟 Ig mRNA 表达、重组激活基因（RAG1 和 RAG2）以及 Th2 炎症和 GC 反应的关键标志物。使用双重或三重免疫荧光（IF）对 NP 组织中的 RAG1 和 RAG2 在 B 细胞、浆细胞和 T 细胞中的共表达进行免疫染色。

结果

与 AR 和正常对照（NC）相比，NP 中的局部 IgE 水平和局部类别转换的关键标志物增加。在 NP 中，转换环转录本揭示了局部类别转换重组到 IgE 的持续进行。高达 30%的 NP 中的 B 细胞、浆细胞和 T 细胞重新表达 RAG1 和 RAG2，这是受体修正所必需的。NP 中的 RAG1 和 RAG2 mRNA 浓度增加，且与炎症程度和鼻息肉黏膜中金黄色葡萄球菌肠毒素（超抗原）特异性 IgE 的存在相关。