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. CONCLUSION: 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. CLINICAL IMPLICATIONS: Our findings reveal prospects for local targeting of the Ig class switch mechanism in the management of atopic and nonatopic 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. CONCLUSION: 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. CLINICAL IMPLICATIONS: Our findings reveal prospects for local targeting of the Ig class switch mechanism in the management of atopic and nonatopic asthma.
Authors: Sumit Ghosh; Scott A Hoselton; Scott V Asbach; Breanne N Steffan; Steve B Wanjara; Glenn P Dorsam; Jane M Schuh Journal: Cell Mol Immunol Date: 2014-11-03 Impact factor: 11.530
Authors: Dong-Young Kim; Sun Hye Lee; Roderick G Carter; Atsushi Kato; Robert P Schleimer; Seong H Cho Journal: Am J Respir Cell Mol Biol Date: 2016-08 Impact factor: 6.914
Authors: M Vicario; C Blanchard; K F Stringer; M H Collins; M K Mingler; A Ahrens; P E Putnam; J P Abonia; J Santos; M E Rothenberg Journal: Gut Date: 2010-01 Impact factor: 23.059