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

被引:177
作者
Takhar, P
Smurthwaite, L
Coker, HA
Fear, DJ
Banfield, GK
Carr, VA
Durham, SR
Gould, HJ
机构
[1] Kings Coll London, Randall Div, London SE1 1UL, England
[2] Univ London Imperial Coll Sci Technol & Med, Sch Med, Natl Heart & Lung Inst, London, England
关键词
D O I
10.4049/jimmunol.174.8.5024
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:5024 / 5032
页数:9
相关论文
共 42 条
[1]  
Cameron L, 2000, J ALLERGY CLIN IMMUN, V106, P46
[2]   SεSμ and SεSγ switch circles in human nasal mucosa following ex vivo allergen challenge:: Evidence for direct as well as sequential class switch recombination [J].
Cameron, L ;
Gounni, AS ;
Frenkiel, S ;
Lavigne, F ;
Vercelli, D ;
Hamid, Q .
JOURNAL OF IMMUNOLOGY, 2003, 171 (07) :3816-3822
[3]   Expression of IL-4, Cε RNA, and Iε RNA in the nasal mucosa of patients with seasonal rhinitis:: Effect of topical corticosteroids [J].
Cameron, LA ;
Durham, SR ;
Jacobson, MR ;
Masuyama, K ;
Juliusson, S ;
Gould, HJ ;
Lowhagen, O ;
Minshall, EM ;
Hamid, OA .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 1998, 101 (03) :330-336
[4]   Ongoing in vivo immunoglobulin class switch DNA recombination in chronic lymphocytic leukemia B cells [J].
Cerutti, A ;
Zan, H ;
Kim, EC ;
Shah, S ;
Schattner, EJ ;
Schaffer, A ;
Casali, P .
JOURNAL OF IMMUNOLOGY, 2002, 169 (11) :6594-6603
[5]   Local somatic hypermutation and class switch recombination in the nasal mucosa of allergic rhinitis patients [J].
Coker, HA ;
Durham, SR ;
Gould, HJ .
JOURNAL OF IMMUNOLOGY, 2003, 171 (10) :5602-5610
[6]   Expression of epsilon germ-line gene transcripts and mRNA for the epsilon heavy chain of IgE in nasal B cells and the effects of topical corticosteroid [J].
Durham, SR ;
Gould, HJ ;
Thienes, CP ;
Jacobson, MR ;
Masuyama, K ;
Rak, S ;
Lowhagen, O ;
Schotman, E ;
Cameron, L ;
Hamid, QA .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1997, 27 (11) :2899-2906
[7]   In situ class switching and differentiation to IgA-producing cells in the gut lamina propria [J].
Fagarasan, S ;
Kinoshita, K ;
Muramatsu, M ;
Ikuta, K ;
Honjo, T .
NATURE, 2001, 413 (6856) :639-643
[8]   Transcription of Ig germline genes in single human B cells and the role of cytokines in isotype determination [J].
Fear, DJ ;
McCloskey, N ;
O'Connor, B ;
Felsenfeld, G ;
Gould, HJ .
JOURNAL OF IMMUNOLOGY, 2004, 173 (07) :4529-4538
[9]  
FOKKENS W J, 1988, Rhinology (Utrecht), V26, P293
[10]  
FUJIEDA S, 1995, J IMMUNOL, V155, P2318