Class switch recombination to IgE in the bronchial mucosa of atopic and nonatopic patients with asthma

• Published in: Journal of Allergy and Clinical Immunology Vol. 119; no. 1; pp. 213 - 218
• Main Authors: Takhar, Pooja, Corrigan, Christopher J., Smurthwaite, Lyn, O'Connor, Brian J., Durham, Stephen R., Lee, Tak H., Gould, Hannah J.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 2007; Elsevier; Elsevier Limited
• Subjects: Adult; AICDA (Activation-Induced Cytidine Deaminase); Allergies; Allergy and Immunology; Asthma; Asthma - genetics; Asthma - immunology; Asthma - metabolism; Biological and medical sciences; Bronchi - immunology; Bronchi - metabolism; class switch recombination; Cytidine Deaminase - genetics; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Hypersensitivity, Immediate - genetics; Hypersensitivity, Immediate - immunology; Hypersensitivity, Immediate - metabolism; IgE; Immunoglobulin Class Switching - genetics; Immunoglobulin E - genetics; Immunoglobulin epsilon-Chains - genetics; Immunopathology; Male; Medical sciences; Middle Aged; mucosa; Recombination, Genetic; Respiratory Mucosa - metabolism; RNA, Messenger - metabolism; United Kingdom > UK; AA; AC; CSR; IgE; asthma; class switch recombination; GLT; CT; NA; NC; SPT; UK; AID; mucosa; Germline gene transcript; Activation-induced cytidine deaminase; Skin prick test; United Kingdom; Nonatopic patient with asthma; Atopic control without asthma; Nonatopic control without asthma; Atopic patient with asthma; Circle transcript; Intrinsic asthma; Human; Allergy; Immunopathology; Lung disease; Recombination; Respiratory disease; Mucosa; Respiratory system; Atopy; Respiratory tract; Immunology; IgE. class switch recombination; Bronchus disease; Obstructive pulmonary disease; Isotype switching
• ISSN: 0091-6749; 1097-6825; 1365-2567
• DOI: 10.1016/j.jaci.2006.09.045

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. 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. We have used RT-PCR to examine ɛ immunoglobulin heavy-chain germline gene transcripts (GLTs; ɛGLTs), ɛ circle transcripts (CTs; Iɛ-Cμ CT or Iɛ-Cγ CT), and mRNA encoding the heavy chain of IgE (ɛ 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). The ɛGLT and AID mRNA were detectable in the bronchial mucosa of subjects in all 4 groups. In contrast, Iɛ-Cμ CT, Iɛ-Cγ CT, and ɛ 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. The bronchial mucosa is a site primed in all individuals for class switching to IgE, because of B-cell expression of ɛGLT and AID mRNA. However, it is only in patients with asthma, regardless of atopic status, that class switching to IgE occurs. Our findings reveal prospects for local targeting of the Ig class switch mechanism in the management of atopic and nonatopic asthma.