Allergen drives class switching to IgE in the nasal mucosa in allergic rhinitis.
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.
Takhar
Pooja
P
The Randall Division, King's College London, London, United Kingdom.
Smurthwaite
Lyn
L
Coker
Heather A
HA
Fear
David J
DJ
Banfield
Graham K
GK
Carr
Victoria A
VA
Durham
Stephen R
SR
Gould
Hannah J
HJ
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)
D000485:Allergens; D018076:DNA, Complementary; D012333:RNA, Messenger; D007073:Immunoglobulin E; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D043525:Cytosine Deaminase; D003564:Cytidine Deaminase