Class switch recombination to IgE in the bronchial mucosa of atopic and nonatopic patients with asthma.
BACKGROUND
Class switching from IgM/IgG/IgA to IgE is required for B cells to express IgE. This requires class switch recombination in the Ig heavy-chain gene locus. It is generally believed that class switch recombination occurs in lymphoid tissue, but it was recently shown that class switching to IgE occurs in the nasal mucosa in allergic rhinitis.


OBJECTIVE
We aimed to determine whether class switching to IgE also occurs in the bronchial mucosa in asthma, and to look for possible differences/similarities between atopic and nonatopic asthma.


METHODS
We have used RT-PCR to examine epsilon immunoglobulin heavy-chain germline gene transcripts (GLTs; epsilonGLTs), epsilon circle transcripts (CTs; Ivarepsilon-Cmu CT or Ivarepsilon-Cgamma CT), and mRNA encoding the heavy chain of IgE (epsilon mRNA) and activation-induced cytidine deaminase (AID) in bronchial biopsies from atopic patients with asthma, nonatopic patients with asthma, atopic controls without asthma, and nonatopic controls without asthma (10 subjects in each group).


RESULTS
The varepsilonGLT and AID mRNA were detectable in the bronchial mucosa of subjects in all 4 groups. In contrast, Iepsilon-Cmu CT, Ivarepsilon-Cgamma CT, and epsilon mRNA were detectable in the bronchial mucosa of the majority of both atopic and nonatopic patients with asthma, but rarely in the controls without asthma.


CONCLUSIONS
The bronchial mucosa is a site primed in all individuals for class switching to IgE, because of B-cell expression of epsilonGLT and AID mRNA. However, it is only in patients with asthma, regardless of atopic status, that class switching to IgE occurs.


CONCLUSIONS
Our findings reveal prospects for local targeting of the Ig class switch mechanism in the management of atopic and nonatopic asthma.
Takhar
Pooja
P
Randall Division of Cell and Molecular Biophysics, King's College London, UK.
Corrigan
Christopher J
CJ
Smurthwaite
Lyn
L
O'Connor
Brian J
BJ
Durham
Stephen R
SR
Lee
Tak H
TH
Gould
Hannah J
HJ
D000328:Adult; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001980:Bronchi / Q000276:immunology / Q000378:metabolism; D003564:Cytidine Deaminase / Q000235:genetics; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D017578:Immunoglobulin Class Switching / Q000235:genetics*; D007073:Immunoglobulin E / Q000235:genetics*; D007139:Immunoglobulin epsilon-Chains / Q000235:genetics; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D011995:Recombination, Genetic; D020545:Respiratory Mucosa / Q000378:metabolism; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D007139:Immunoglobulin epsilon-Chains; D012333:RNA, Messenger; D007073:Immunoglobulin E; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase