title: Allergen drives class switching to IgE in the nasal mucosa in allergic rhinitis.
abstract: 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 epsilon 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 epsilon 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.
authors.affiliation: The Randall Division, King's College London, London, United Kingdom.
authors.forename: Pooja
authors.initials: P
authors.lastname: Takhar
authors.forename: Lyn
authors.initials: L
authors.lastname: Smurthwaite
authors.forename: Heather A
authors.initials: HA
authors.lastname: Coker
authors.forename: David J
authors.initials: DJ
authors.lastname: Fear
authors.forename: Graham K
authors.initials: GK
authors.lastname: Banfield
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Carr
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Durham
authors.forename: Hannah J
authors.initials: HJ
authors.lastname: Gould
mesh_terms: D000328:Adult; D000485:Allergens / Q000008:administration & dosage*; D001402:B-Lymphocytes / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D001483:Base Sequence; D016022:Case-Control Studies; D003564:Cytidine Deaminase; D043525:Cytosine Deaminase / Q000235:genetics / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D006801:Humans; D017578:Immunoglobulin Class Switching; D007073:Immunoglobulin E / Q000235:genetics*; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009297:Nasal Mucosa / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012221:Rhinitis, Allergic, Perennial / Q000201:enzymology / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D006255:Rhinitis, Allergic, Seasonal / Q000201:enzymology / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D012689:Sequence Homology, Nucleic Acid; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D000485:Allergens; D018076:DNA, Complementary; D012333:RNA, Messenger; D007073:Immunoglobulin E; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D043525:Cytosine Deaminase; D003564:Cytidine Deaminase