Basic and clinical immunologyClass switch recombination to IgE in the bronchial mucosa of atopic and nonatopic patients with asthma
Section snippets
Clinical protocol
Bronchial biopsies were obtained at fiberoptic bronchoscopy from atopic patients with asthma (AAs), nonatopic patients with asthma (NAs), atopic controls without asthma (ACs), and nonatopic controls without asthma (NCs; n = 10 in each group). Asthma was defined as a clear history of relevant symptoms with either reversible airways obstruction (≥15% variability in the FEV1 either spontaneously or after inhaled albuterol, 200 μg), and/or a histamine PC20 provocation test result <8 mg/mL
ɛGLT expression in the bronchial mucosa
ɛ Germline transcription marks the first step in the commitment of B cells to the synthesis of IgE. We sought ɛGLT in bronchial mucosal biopsies from 10 patients in each of the 4 subject groups. As shown in Fig 1, A, and Table II, ɛGLT expression was detected in 8 of 10 AAs, 7 of 10 NAs, 5 of 10 ACs, and 1 of 10 NCs.
ɛCT expression in the bronchial mucosa
DNA recombination, producing ɛCT, marks the irreversible step in the commitment of B cells to the synthesis of IgE. We sought ɛCT in the same biopsies used to detect GLT. IgM to IgE
Discussion
We have investigated B-cell IgE switching and synthesis in the bronchial mucosa of patients with asthma, and provide the first direct and definitive evidence that bronchial mucosal B cells undergo class switch recombination from IgM and IgG to IgE in situ. Our data would suggest that this phenomenon is a particular feature of asthma, and occurs irrespective of the atopic status of the patients with asthma as assigned by conventional SPT or in vitro testing to detect allergen-specific IgE. The
References (22)
- et al.
The immunopathology of extrinsic (atopic) and intrinsic (non-atopic) asthma: more similarities than differences
Immunol Today
(1999) - et al.
Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme
Cell
(2000) - et al.
Specific expression of activation-induced cytidine deaminase (AID), a novel member of the RNA-editing deaminase family in germinal center B cells
J Biol Chem
(1999) - et al.
Elevated expression of messenger ribonucleic acid encoding IL-13 in the bronchial mucosa of atopic and nonatopic subjects with asthma
J Allergy Clin Immunol
(1997) - et al.
Local expression of ɛ germline gene transcripts and RNA for the ɛ heavy chain of IgE in the bronchial mucosa in atopic and nonatopic asthma
J Allergy Clin Immunol
(2001) - et al.
Germinal-centre reactions in allergic inflammation
Trends Immunol
(2006) - et al.
The anti-inflammatory effects of omalizumab confirm the central role of IgE in allergic inflammation
J Allergy Clin Immunol
(2005) - et al.
The biology of IgE and the basis of allergic disease
Annu Rev Immunol
(2003) - et al.
Allergic and nonallergic asthma: still a matter for debate?
Clin Asthma Rev
(1997) Mechanisms of intrinsic asthma
Curr Opin Allergy Clin Immunol
(2004)
The continuing enigma of non-atopic asthma
Clin Exp Allergy
Cited by (201)
MZB1-expressing cells are essential for local immunoglobulin production in chronic rhinosinusitis with nasal polyps
2024, Annals of Allergy, Asthma and ImmunologyAllergen Immunotherapy for Asthma
2024, Journal of Allergy and Clinical Immunology: In PracticeClonal evolution and stereotyped sequences of human IgE lineages in aeroallergen-specific immunotherapy
2023, Journal of Allergy and Clinical ImmunologyCellular and molecular mechanisms of allergic asthma
2022, Molecular Aspects of MedicineCitation Excerpt :In strong type 2 inflammatory responses of the lung, germinal centers are prevalent in ELAs and contain IgE-producing B cells (Chvatchko et al., 1996; Slavin et al., 1992). IgE-producing B cells may also undergo affinity maturation and clonal selection in the bronchus-associated lymphoid tissue (BALT, the pulmonary ELA) in patients with asthma (Takhar et al., 2007). ILC2s (Fukuoka et al., 2013) and neuropilin-1-expressing ILC3-like cells (Shikhagaie et al., 2017) may have a role in the organization of BALT with IgE-producing capacity.
A review of hypersensitivity methods to detect immune responses to SARS-CoV-2
2022, Methods in MicrobiologyCitation Excerpt :B cells recognize allergenic molecules through their B-cell receptor (BCR) and are triggered by the TH2 cytokines Il-4 and Il-13 to undergo class–switch recombination to IgE (and IgG4)-producing cells (De Vries, Punnonen, Cocks, de Waal Malefyt, & Aversa, 1993). The encounter between TH2 and the B cells occurs both in lymphoid germinal centres and in local mucosal sites (respiratory mucosa) (Takhar et al., 2007). Once released into the circulation, most of the produced IgE binds to the high-affinity receptor FcɛRI on the surface of mast cells and basophiles (Metzger, Kinet, Blank, Miller, & Ra, 1989).
Supported by Asthma UK Grant #03/055 and MRC Cooperative Component Grant #G0200485.
Disclosure of potential conflict of interest: H. J. Gould and P. Takhar have received grant support from Asthma UK and the Medical Research Council. L. Smurthwaite is now employed by Asthma UK but at the time of contributing to this article was not in their employment. B. J. O'Connor has consulting arrangements with GlaxoSmithKline, AstraZeneca, Altana, Celgene, Pfizer, Boehringer Ingelheim, Inflazyme, NiCox, Theravance, Pharmadigm, and Inverseon; has received grant support from GlaxoSmithKline, AstraZeneca, Altana, Aventis, Novartis, Pfizer, Inflazyme, NiCox, Pharmadigm, and Oxagen; and is on the speakers' bureau for AstraZeneca, GlaxoSmithKline, Pfizer, Bushranger Ingelheim, and Altana. S. R. Durham has consulting arrangements with ALK-Abelló, GlaxoSmithKline, and Novartis, has received grant support from ALK-Abelló, GlaxoSmithKline, and UCB; and is on the speakers' bureau for ALK-Abelló and Allergy Therapeutics. The rest of the authors have declared that they have no conflict of interest.