Nasal mast cells in perennial allergic rhinitics exhibit increased expression of the Fc epsilonRI, CD40L, IL-4, and IL-13, and can induce IgE synthesis in B cells.

Pawankar, Ruby; Okuda, Masahiro; Yssel, Hans; Okumura, Ko; Ra, Chisei

doi:10.1172/jci119311

Cited by 315 publications

(228 citation statements)

References 31 publications

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“…Similar observations of isotype switching have been made by SAXON et al [22] in nasal mucosal cells. Not only T-cells but also mast cells and basophils have the capacity to stimulate IgE synthesis by B-cells, as producers of IL-4 and IL-13 and by the interaction of mast cells CD154 (CD40 ligand) with B-cell CD40 [18,30,31]. The mast cell/basophilic induction and stimulation of B-cell IgE-production indicate that immunoglobulin switching, previously thought to take place only in lymph node germinal centres, may also occur in peripheral organs such as the nose.…”

Section: Discussionmentioning

confidence: 99%

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Local production and detection of (specific) IgE in nasal B-cells and plasma cells of allergic rhinitis patients

et al. 2000

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Allergic diseases are characterized by allergic complaints in the shock organ and specific immunoglobulin (Ig)E in serum. Literature data indicate that the nasal mucosa itself could produce at least a large part of the specific IgE in allergic rhinitis patients.In order to investigate this hypothesis, nasal mucosal biopsies from the inferior turbinate were taken from symptomatic grass pollen allergic rhinitis patients, symptomatic house dust mite allergic rhinitis patients and nonallergic healthy controls, confirmed by radioallergosorbent test and skin-prick test. Immunohistochemical double-staining was performed for B-cells (CD19) with IgE, plasma cells (CD138) with IgE and plasma cells with biotinylated allergens.Significantly more IgE-positive B-cells and IgE-positive plasma cells were found in the nasal mucosa of allergic patients than in that of nonallergic controls. Double staining with biotinylated allergens and plasma cells showed allergen-positive plasma cells in the nasal mucosa of allergic patients and no allergen-positive plasma cells in the nasal mucosa of nonallergic patients. Blocking experiments using polyclonal antibodies directed against IgE showed a significant reduction in the number of allergenpositive cells in contrast to experiments using polyclonal antibodies directed against IgG, IgA or IgM.This study describes new evidence that specific immunoglobulin E is produced locally in the nasal mucosa in patients with seasonal allergic rhinitis and perennial allergic rhinitis, but not in nonallergic controls. Eur Respir J 2000; 15: 491±497.

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Section: Discussionmentioning

confidence: 99%

“…They were not able to detect IgE-positive B-cells. PAWANKAR et al [18] suggested novel and critical roles for mast cells obtained from allergic rhinitis patients in amplifying IgE production, within the local microenvironment of the nasal mucosa.…”

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Local production and detection of (specific) IgE in nasal B-cells and plasma cells of allergic rhinitis patients

et al. 2000

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“…A further requirement for CSR in primary B cells is CD40 signaling (12,17). Allergen stimulates the expression of IL-4 and CD40 ligand by Th2 cells and mast cells in the nasal mucosa in allergic rhinitis (18,19). Thus, we have reason to suggest that aeroallergens might stimulate the expression of AID and CSR to IgE in the nasal mucosa in allergic rhinitis.…”

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confidence: 99%

Allergen Drives Class Switching to IgE in the Nasal Mucosa in Allergic Rhinitis

Takhar

Smurthwaite

Coker

et al. 2005

The Journal of Immunology

197

187

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IgE-expressing B cells are over 1000 times more frequent in the nasal B cell than the peripheral blood B cell population. We have investigated the provenance of these B cells in the nasal mucosa in allergic rhinitis. It is generally accepted that expression of activation-induced cytidine deaminase and class switch recombination (CSR) occur in lymphoid tissue, implying that IgE-committed B cells must migrate through the circulation to the nasal mucosa. Our detection of mRNA for activation-induced cytidine, multiple germline gene transcripts, and ε circle transcripts in the nasal mucosa of allergic, in contrast to nonallergic control subjects, however, indicates that local CSR occurs in allergic rhinitis. The germline gene transcripts and ε circle transcripts in grass pollen-allergic subjects are up-regulated during the season and also when biopsies from allergic subjects are incubated with the allergen ex vivo. These results demonstrate that allergen stimulates local CSR to IgE, revealing a potential target for topical therapies in allergic rhinitis.

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“…Activation of these cells results in the release of spasmogenic and vasoactive mediators as well as chemical mediators that promote infiltration of other leukocytes, including eosinophils, to sites of inflammation (6). Mast cells can signal naive and memory T cells to preferentially differentiate into Th2 cells (7) and induce IgE synthesis in B cells (8). It has also been reported that activation of mast cells in the airways of mice by anti-IgE Ab results in enhanced airway responsiveness to cholinergic stimulation by methacholine (9).…”

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confidence: 99%

IgE-Dependent Mast Cell Activation Potentiates Airway Responses in Murine Asthma Models

Mayr

Zuberi

Zhang

et al. 2002

The Journal of Immunology

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We have studied murine models of asthma using FcεRIα-chain-deficient (FcεRIα−/−) mice to investigate the role of IgE-dependent mast cell activation in these models. When mice were either 1) immunized once with OVA in alum i.p. and then challenged with OVA intranasally, or 2) repeatedly immunized with OVA in the absence of adjuvant and subsequently challenged with nebulized OVA, FcεRα−/− mice had significantly fewer eosinophils and lower IL-4 levels in their bronchoalveolar lavage fluid compared with wild-type mice. When mice were given anti-IL-5 antibody before OVA challenge in protocol 1, eosinophilic infiltration into the airways was significantly suppressed in both genotypes, but only FcεRIα−/− mice showed significantly reduced airway hyperresponsiveness (AHR). In addition, when mice immunized and challenged with OVA also received a late OVA provocation at a higher concentration and were then exposed to methacholine, only wild-type mice developed a substantial increase in AHR. Since FcεRI is expressed mainly on mast cells in mouse airways, we conclude that IgE-dependent activation of this cell type plays an important role in the development of allergic airway inflammation and AHR in mice. The models used may be of value for testing inhibitors of IgE or mast cells for development of therapeutic agents for human asthma.

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Nasal mast cells in perennial allergic rhinitics exhibit increased expression of the Fc epsilonRI, CD40L, IL-4, and IL-13, and can induce IgE synthesis in B cells.

Cited by 315 publications

References 31 publications

Local production and detection of (specific) IgE in nasal B-cells and plasma cells of allergic rhinitis patients

Local production and detection of (specific) IgE in nasal B-cells and plasma cells of allergic rhinitis patients

Allergen Drives Class Switching to IgE in the Nasal Mucosa in Allergic Rhinitis

IgE-Dependent Mast Cell Activation Potentiates Airway Responses in Murine Asthma Models

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