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.
We have studied the expression of the gene encoding the epsilon heavy chain of IgE in nasal B cells of hayfever patients. We developed probes to detect transcripts of the epsilon germ-line gene and the rearranged gene by in situ hybridization of biopsy sections from the nasal mucosa. We compared tissue from hayfever patients out of season with that of normal controls, and also of hayfever patients treated with topical corticosteroid (fluticasone propionate) or placebo for 6 weeks and then challenged with antigen. epsilon chain mRNA was expressed in an unexpectedly high proportion of nasal B cells of both hayfever patients and normal subjects. However, although similar numbers of B cells were found in both groups, the proportion of cells that express epsilon chain mRNA was several times higher in the hayfever patients. No transcripts of the epsilon germ-line gene were detected in either group before allergen challenge. When hayfever patients were administered antigen locally, early (10-30 min) and late (1-24 h) symptoms ensued. After 24 h, coincident with an increase in the number of cells expressing mRNA for IL-4 in the tissue, epsilon germ-line gene transcripts appeared in the nasal B cells. The induction by allergen of IL-4 mRNA and epsilon germ-line gene transcripts was suppressed by fluticasone propionate treatment. Our results suggest that local IgE synthesis and cytokine regulation of heavy chain switching to IgE occur in the nasal mucosa.
Durham
S R
SR
Imperial College School of Medicine, National Heart and Lung Institute, London, GB.
Gould
H J
HJ
Thienes
C P
CP
Jacobson
M R
MR
Masuyama
K
K
Rak
S
S
Lowhagen
O
O
Schotman
E
E
Cameron
L
L
Hamid
Q A
QA
D000287:Administration, Topical; D000328:Adult; D000485:Allergens / Q000008:administration & dosage; D000730:Androstadienes / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005260:Female; D000068298:Fluticasone; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D005803:Genes, Immunoglobulin / Q000187:drug effects; D005938:Glucocorticoids; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000235:genetics; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*; D007139:Immunoglobulin epsilon-Chains / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D009297:Nasal Mucosa / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000187:drug effects; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy / Q000276:immunology; D014158:Transcription, Genetic / Q000187:drug effects / Q000276:immunology*
D000485:Allergens; D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D007127:Immunoglobulin Constant Regions; D007139:Immunoglobulin epsilon-Chains; D012333:RNA, Messenger; D015847:Interleukin-4; D007073:Immunoglobulin E; D000068298:Fluticasone