These authors contributed equally to this manuscript.
Local receptor revision and class switching to IgE in chronic rhinosinusitis with nasal polyps
Article first published online: 15 NOV 2012
© 2012 John Wiley & Sons A/S
Volume 68, Issue 1, pages 55–63, January 2013
How to Cite
Local receptor revision and class switching to IgE in chronic rhinosinusitis with nasal polyps. Allergy 2012; DOI: 10.1111/all.12054., , , , , , , , , , , , .
Edited by: Wytske Fokkens
- Issue published online: 4 DEC 2012
- Article first published online: 15 NOV 2012
- Manuscript Accepted: 20 SEP 2012
- allergic rhinitis;
- germinal center-like structures;
- nasal polyps;
- receptor revision
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.
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).
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.
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.