Allergen Drives Class Switching to IgE in the Nasal Mucosa in Allergic Rhinitis

• Published in: The Journal of immunology (1950) Vol. 174; no. 8; pp. 5024 - 5032
• Main Authors: Takhar, Pooja, Smurthwaite, Lyn, Coker, Heather A, Fear, David J, Banfield, Graham K, Carr, Victoria A, Durham, Stephen R, Gould, Hannah J
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.04.2005
• Subjects: Adult; Allergens - administration & dosage; B-Lymphocytes - enzymology; B-Lymphocytes - immunology; B-Lymphocytes - pathology; Base Sequence; Case-Control Studies; Cytidine Deaminase; Cytosine Deaminase - genetics; Cytosine Deaminase - metabolism; DNA, Complementary - genetics; Female; Humans; Immunoglobulin Class Switching; Immunoglobulin E - genetics; In Vitro Techniques; Male; Middle Aged; Molecular Sequence Data; Nasal Mucosa - enzymology; Nasal Mucosa - immunology; Nasal Mucosa - pathology; Rhinitis, Allergic, Perennial - enzymology; Rhinitis, Allergic, Perennial - genetics; Rhinitis, Allergic, Perennial - immunology; Rhinitis, Allergic, Perennial - pathology; Rhinitis, Allergic, Seasonal - enzymology; Rhinitis, Allergic, Seasonal - genetics; Rhinitis, Allergic, Seasonal - immunology; Rhinitis, Allergic, Seasonal - pathology; RNA, Messenger - genetics; RNA, Messenger - metabolism; Sequence Homology, Nucleic Acid
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.174.8.5024

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 ε 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 ε 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.