Allergen drives class switching to IgE in the nasal mucosa in allergic rhinitis

Allergen drives class switching to IgE in the nasal mucosa in allergic rhinitis
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DOI:
10.4049/jimmunol.174.8.5024
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发表时间:
2005-04-15
影响因子:
4.4
通讯作者:
Gould, HJ
Gould, HJ
中科院分区:
医学2区
文献类型:
--
作者:
Takhar, P;Smurthwaite, L;Gould, HJ

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鼻部B细胞中表达免疫球蛋白E的B细胞是外周血B细胞的1000多倍。我们研究了变应性鼻炎鼻粘膜中这些B细胞的来源。一般认为,淋巴组织中存在活化诱导型胞苷脱氨酶和类转换重组(CSR)的表达,这意味着IgE承诺的B细胞必须通过循环迁移到鼻黏膜。然而,与非过敏对照组相比,我们在变应性鼻炎鼻黏膜中检测到激活诱导胞苷、多个生殖系基因转录本和E环转录物的mRNA,然而,表明变应性鼻炎发生了局部CSR。草花粉过敏受试者的生殖系基因转录本和E环转录本在季节以及过敏受试者的活检组织与过敏原体外孵育时也上调。这些结果表明,变应原刺激局部CSR到IgE,揭示了变应性鼻炎局部治疗的潜在靶点。
IgE-expressing B cells are over 1000 times more frequent in the nasal B cell than the peripheral blood B cell population. We have investigated the provenance of these B cells in the nasal mucosa in allergic rhinitis. It is generally accepted that expression of activation-induced cytidine deaminase and class switch recombination (CSR) occur in lymphoid tissue, implying that IgE-committed B cells must migrate through the circulation to the nasal mucosa. Our detection of mRNA for activation-induced cytidine, multiple germline gene transcripts, and E circle transcripts in the nasal mucosa of allergic, in contrast to nonallergic control subjects, however, indicates that local CSR occurs in allergic rhinitis. The germline gene transcripts and E circle transcripts in grass pollen-allergic subjects are up-regulated during the season and also when biopsies from allergic subjects are incubated with the allergen ex vivo. These results demonstrate that allergen stimulates local CSR to IgE, revealing a potential target for topical therapies in allergic rhinitis.