B Cell Antigen Presentation Promotes Th2 Responses and Immunopathology during Chronic Allergic Lung Disease (original) (raw)
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Regulatory functions of B cells in allergic diseases
Allergy, 2014
B cells are essentially described for their capacity to produce antibodies ensuring anti-infectious immunity or deleterious responses in the case of autoimmunity or allergy. However, abundant data described their ability to restrain inflammation by diverse mechanisms. In allergy, some regulatory B-cell subsets producing IL-10 have been recently described as potent suppressive cells able to restrain inflammatory responses both in vitro and in vivo by regulatory T-cell differentiation or directly inhibiting T-cell-mediated inflammation. A specific deficit in regulatory B cells participates to more severe allergic inflammation. Induction of allergen tolerance through specific immunotherapy induces a specific expansion of these cells supporting their role in establishment of allergen tolerance. However, the regulatory functions carried out by B cells are not exclusively IL-10 dependent. Indeed, other regulatory mechanisms mediated by B cells are (i) the production of TGF-b, (ii) the promotion of T-cell apoptosis by Fas-Fas ligand or granzyme-B pathways, and (iii) their capacity to produce inhibitory IgG4 and sialylated IgG able to mediate anti-inflammatory mechanisms. This points to Bregs as interesting targets for the development of new therapies to induce allergen tolerance. In this review, we highlight advances in the study of regulatory mechanisms mediated by B cells and outline what is known about their phenotype as well as their suppressive role in allergy from studies in both mice and humans.
PloS one, 2015
Humans are frequently exposed to various airborne allergens. In addition to producing antibodies, B cells participate in immune responses via various mechanisms. The roles of B cells in allergic airway inflammation and asthma have been controversial. We examined the functional importance of B cells in a mouse model of asthma, in which mice were exposed repeatedly to common airborne allergens. Naïve wild-type BALB/c mice or B cell-deficient JH-/- mice were exposed intranasally to a cocktail of allergen extracts, including Alternaria, Aspergillus, and house dust mite, every other day for two weeks. Ovalbumin was included in the cocktail to monitor the T cell immune response. Airway inflammation, lung pathology, and airway reactivity were analyzed. The airway exposure of naïve wild type mice to airborne allergens induced robust eosinophilic airway inflammation, increased the levels of Th2 cytokines and chemokines in the lung, and increased the reactivity to inhaled methacholine. These ...
Regulatory Role of B Cells In a Murine Model of Allergic Airway Disease
The Journal of …, 2008
Mice sensitized to OVA and subjected to acute OVA aerosol exposures develop allergic airway disease (AAD). However, chronic continuous Ag exposure results in resolution of AAD and the development of local inhalational tolerance (LIT). Because we have previously observed ...
Frontiers in Immunology, 2021
In order to better understand how the immune system interacts with environmental triggers to produce organ-specific disease, we here address the hypothesis that B and plasma cells are free to migrate through the mucosal surfaces of the upper and lower respiratory tracts, and that their total antibody repertoire is modified in a common respiratory tract disease, in this case atopic asthma. Using Adaptive Immune Receptor Repertoire sequencing (AIRR-seq) we have catalogued the antibody repertoires of B cell clones retrieved near contemporaneously from multiple sites in the upper and lower respiratory tract mucosa of adult volunteers with atopic asthma and non-atopic controls and traced their migration. We show that the lower and upper respiratory tracts are immunologically connected, with trafficking of B cells directionally biased from the upper to the lower respiratory tract and points of selection when migrating from the nasal mucosa and into the bronchial mucosa. The repertoires ar...
Role of regulatory B cells in immune tolerance to allergens and beyond
The Journal of allergy and clinical immunology, 2016
Immune tolerance to both self-antigens and innocuous non-self-antigens is essential to protect the host against chronic inflammatory diseases and tissue damage. A wide range of cell types and suppressive molecules are involved in induction and maintenance of tolerance. In addition to their key function in the production of immunoglobulins, B cells can regulate immune responses through their surface molecules and secretion of cytokines. Regulatory B (Breg) cells are characterized by their immunosuppressive capacity, which is often mediated through IL-10 secretion. However, IL-35 and TGF-β have also been associated with B cell-mediated immunosuppression. Several types of murine and human Breg cells have been described, such as mouse CD5(+)CD1d(hi) B10 cells, CD21(hi)CD23(hi)CD24(hi) transitional stage 2-like B cells, and CD138(+) plasma cells and plasmablasts. Human Breg cell types include CD27(+)CD24(high) B10 cells, CD24(hi)CD38(hi) immature transitional B cells, and CD73(-)CD25(+)C...
Proceedings of the National Academy of Sciences, 1997
B cells play an important role in the allergic response by producing allergen-specific Igs as well as by serving as antigen-presenting cells. We studied the involvement of B cells in the development of responses in a murine model of allergic airway sensitization. Normal and B celldeficient (Mt ؊͞؊ ) B10.BR mice were sensitized via the airways to ovalbumin; Ig production, cytokine elaboration from local lymph node cells, development of airway hyperresponsiveness, and histological changes in the airways were evaluated. Both strains of mice had increased production of T helper 2-like cytokines and developed an accumulation of eosinophils in the bronchial tissue after airway sensitization. However, only wild-type mice produced allergen-specific antibodies and exhibited altered airway function. B cell-deficient mice reconstituted with anti-ovalbumin IgE during the course of sensitization developed increases in airway responsiveness. These results indicated that neither B cells nor IgE were necessary for the induction of a T helper 2-type cytokine response or eosinophil infiltration of the airways after allergic sensitization but that IgE was required as a second signal for the development of airway hyperresponsiveness in this model of airway sensitization.
Alterations on peripheral blood B cell subsets induced by allergic rhinitis
Inflammation Research, 2015
Objectives and design Here we evaluated whether allergic rhinitis to Dermatophagoides pteronyssinus induces alterations on circulating B cell subsets. Materials and methods Circulating B cell subsets and isotype expression on antigen-experienced B cells from allergic patients under conventional pharmacological treatment (NO-SIT, n = 15) and under subcutaneous immunotherapy (SCIT, n = 33), and non-allergic subjects (NC, n = 25) were analyzed by flow cytometry. Results In allergic patients, we found a significant decrease in IgM ? and IgG ? memory B cells and an increase in IgA ? memory B cells. Additionally, the numbers of circulating IgA ? plasmablasts in allergic patients were also increased, while those cells expressing IgM were reduced. Conclusions Allergic patients have a disturbed B cell subsets distribution which seems to underlie rhinitis pathogenesis and remain unchanged after SCIT.
Critical role of B cells in the development of T cell tolerance to aeroallergens
International Immunology, 2002
Respiratory exposure to allergen induces the development of allergen-speci®c CD4 + T cell tolerance that effectively protects against the development of allergic-sensitization and T h 2-biased immunity. The establishment of T cell unresponsiveness to aeroallergens is an active process preceded by a transient phase of T cell activation that requires T cell co-stimulation and is critically in¯uenced by the antigen-presenting cell type. In this study we examined the role of B cells in the development of respiratory tolerance following intranasal (i.n.) exposure to a prototypic protein antigen. We found that respiratory exposure of BCR-transgenic (Tg) mice to minute quantities of cognate antigen effectively induced T cell unresponsiveness, indicating that antigen presentation by antigen-speci®c B cells greatly enhanced the development of respiratory tolerance. In contrast, respiratory T cell unresponsiveness could not be induced in B cell-de®cient JHD mice exposed to i.n. antigen, although T cell tolerance developed in JHD mice reconstituted with B cells, suggesting that B cells are required for the induction of respiratory T cell tolerance. Respiratory exposure of BCR-Tg mice to cognate antigen induced activation of antigen-speci®c T cells and partial activation of antigen-speci®c B cells, as demonstrated by enhanced expression by B cells of class II MHC and B7 molecules but lack of antibody secretion. Our data indicate that B cells critically in¯uence the immune response to inhaled allergens and are required for the development of allergen-speci®c T cell unresponsiveness induced by respiratory allergen.
Clinical & Experimental Allergy, 2014
Background Regulatory B cells have been identified that strongly reduce allergic and auto-immune inflammation in experimental models by producing IL-10. Recently, several human regulatory B-cell subsets with an impaired function in auto-immunity have been described, but there is no information on regulatory B cells in allergic asthma. Objective In this study, the frequency and function of IL-10 producing B-cell subsets in allergic asthma were investigated. Methods Isolated peripheral blood B cells from 13 patients with allergic asthma and matched healthy controls were analyzed for the expression of different regulatory B-cell markers. Next, the B cells were activated by lipopolysaccharide (LPS), CpG or through the B-cell receptor, followed by co-culture with endogenous memory CD4 + T cells and house dust mite allergen DerP1. Results Lower number of IL-10 producing B cells were found in patients in response to LPS, however, this was not the case when B cells were activated through the B-cell receptor or by CpG. Further dissection showed that only the CD24 hi CD27 + B-cell subset was reduced in number and IL-10 production to LPS. In response to DerP1, CD4 + T cells from patients co-cultured with LPS-primed total B cells produced less IL-10 compared to similar cultures from controls. These results are in line with the finding that sorted CD24 hi CD27 + B cells are responsible for the induction of IL-10 + CD4 + T cells.