Role of regulatory B cells in immune tolerance to allergens and beyond (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.
Il-10 producing T and B cells in allergy
Seminars in Immunology, 2019
The molecular and cellular mechanisms of allergen tolerance in humans have been intensively studied in the past few decades. The demonstration of epitope-specific T cell tolerance, particularly mediated by the immune suppressor functions of IL-10 led to a major conceptual change in this area more than 20 years ago. Currently, the known essential components of allergen tolerance include the induction of allergen-specific regulatory of T and B cells, the immune suppressive function of secreted factors, such as IL-10, IL-35, IL-1 receptor antagonist and TGF-β, immune suppressive functions of surface molecules such as CTLA-4 and PD-1, the production IgG4 isotype allergen-specific blocking antibodies, and decreased allergic inflammatory responses by mast cells, basophils, and eosinophils in inflamed tissues. In this review, we explain the importance of the role of IL-10 in allergen tolerance.
Regulatory B cells that produce IL-10: A breath of fresh air in allergic airway disease
Journal of Allergy and Clinical Immunology, 2010
Asthma; regulatory B cell In this issue of the Journal of Allergy and Clinical Immunology, Amu and colleagues demonstrate a significant role for interleukin-10 (IL-10)-producing regulatory B (Breg) cells during mouse models of allergic airway inflammation 1 . The authors identified a Breg cell subpopulation that expands in vivo and in vitro in response to parasitic Schistosoma mansoni worm infection. The adoptive transfer of these Breg cells into allergen-sensitized mice suppresses anaphylaxis and allergen-induced airway hyper-responsiveness through IL-10dependent mechanisms 1, 2 . These important findings expand the clinical significance of studies showing that IL-10-competent Breg cells dramatically regulate inflammation and autoimmunity in mouse models of contact hypersensitivity 3 , experimental autoimmune encephalomyelitis (EAE) 4, 5 , collagen induced arthritis 6 , and inflammatory bowel disease 7 .
Allergen extract-induced interleukin-10 in human memory B cells inhibits immunoglobulin E production
Clinical & Experimental Allergy, 2009
Background Elevated specific IgE antibody levels are common in atopic individuals, caused by T-helper type 2-dominated B cell activation. The induction of antigen-specific IL-10 secreting T cells is discussed as an important mechanism during specific immunotherapy. By contrast the presence and function of B cell-derived IL-10 is not well defined yet. Objective We investigated whether type-I allergen extracts induce IL-10 expression in human B cells and analysed its functional role on IgE production. Methods Human peripheral B cells were stimulated with grass pollen, house dust mite (HDM) (Dermatophagoides pteronyssimus; Der p) and dog allergen extract. Expression of IL-10 by activated human B cells was determined by flow cytometric analysis and ELISA. Functional analysis considering immunoglobulin production was assayed by ELISA. Results The allergen extracts studied induced IL-10 expression in B cells. However, the ability to induce IL-10 differed between the allergen extracts. The most potent allergen extract was dog (169AE28 pg/mL), followed by grass pollen (141AE10 pg/mL) and HDM allergen (125AE11 pg/mL). Upon allergen extract stimulation only CD27 expressing memory B cells produced IL-10 and co-expressed the very early activation antigen CD69. The addition of allergen extracts to B cells activated by anti-CD40 and IL-4 selectively inhibited IgE which was dependent on allergen extract-induced IL-10. By contrast the other immunoglobulin subclasses like IgA, IgG or IgM were not altered upon allergen extract challenge. Conclusion Our data indicate that allergen-activated memory B cells can modulate IgE production through secretion of IL-10.
Tolerogenic property of B-1b cells in a model of allergic reaction
Immunology letters, 2007
Since B-1 cells were first described, their origin and function remain controversial. Given the ability to produce natural antibodies and large amounts of IL-10, there is a consensus about their role in innate immunity. More recently, however, B-1 cells have been associated to ...
Regulatory T cells and immune regulation of allergic diseases: roles of IL-10 and TGF-β
Genes and Immunity, 2014
The prevalence of allergic diseases has significantly increased in industrialized countries. Allergen-specific immunotherapy (AIT) remains as the only curative treatment. The knowledge about the mechanisms underlying healthy immune responses to allergens, the development of allergic reactions and restoration of appropriate immune responses to allergens has significantly improved over the last decades. It is now well-accepted that the generation and maintenance of functional allergen-specific regulatory T (Treg) cells and regulatory B (Breg) cells are essential for healthy immune responses to environmental proteins and successful AIT. Treg cells comprise different subsets of T cells with suppressive capacity, which control the development and maintenance of allergic diseases by various ways of action. Molecular mechanisms of generation of Treg cells, the identification of novel immunological organs, where this might occur in vivo, such as tonsils, and related epigenetic mechanisms are starting to be deciphered. The key role played by the suppressor cytokines interleukin (IL)-10 and transforming growth factor (TGF)-b produced by functional Treg cells during the generation of immune tolerance to allergens is now well established. Treg and Breg cells together have a role in suppression of IgE and induction of IgG4 isotype allergen-specific antibodies particularly mediated by IL-10. Other cell types such as subsets of dendritic cells, NK-T cells and natural killer cells producing high levels of IL-10 may also contribute to the generation of healthy immune responses to allergens. In conclusion, better understanding of the immune regulatory mechanisms operating at different stages of allergic diseases will significantly help the development of better diagnostic and predictive biomarkers and therapeutic interventions.
PLoS ONE, 2008
Background: The role of B cells in allergic asthma remains undefined. One mechanism by which B cells clearly contribute to allergic disease is via the production of specific immunoglobulin, and especially IgE. Cognate interactions with specific T cells result in T cell help for B cells, resulting in differentiation and immunoglobulin secretion. Proximal to (and required for) T cell-dependent immunoglobulin production, however, is antigen presentation by B cells. While interaction with T cells clearly has implications for B cell function and differentiation, this study investigated the role that B cells have in shaping the T cell response during chronic allergic lung disease.
Journal of Allergy and Clinical Immunology, 2013
Background: IL-10-producing regulatory B cells suppress immune responses, and lack of these cells leads to exacerbated symptoms in mouse models of chronic inflammation, transplantation, and chronic infection. IgG 4 is a blocking antibody isotype with anti-inflammatory potential that is induced in human high-dose antigen tolerance models. Objective: We sought to characterize human inducible IL-10secreting B regulatory 1 (B R 1) cells and to investigate their immunoregulatory capacity through suppression of cellular immune responses and production of anti-inflammatory immunoglobulins. Methods: Highly purified IL-10-secreting B cells were phenotypically and functionally characterized by means of whole-genome expression analysis, flow cytometry, suppression assay, and antibody production. B cells specific for the major bee venom allergen phospholipase A 2 (PLA) were isolated from beekeepers who displayed tolerance to bee venom antigens and allergic patients before and after specific immunotherapy. Results: Human IL-10 1 B R 1 cells expressed high surface CD25 and CD71 and low CD73 levels. Sorting of CD73 2 CD25 1 CD71 1 B cells allowed enrichment of human B R 1 cells, which produced high levels of IL-10 and potently suppressed antigen-specific CD4 1 T-cell proliferation. IgG 4 was selectively confined to human B R 1 cells. B cells specific for the major bee venom allergen PLA isolated from nonallergic beekeepers show increased expression of IL-10 and IgG 4 . Furthermore, the frequency of IL-10 1 PLA-specific B cells increased in allergic patients receiving allergen-specific immunotherapy. Conclusion: Our data show the characterization of IL-10 1 B R 1 cells and in vivo evidence for 2 essential features of allergen tolerance: the suppressive B cells and IgG 4 -expressing B cells that are confined to IL-10 1 B R 1 cells in human subjects. (J Allergy Clin Immunol 2013;131:1204-12.)
B cells and immunological tolerance
The Journal of investigative dermatology, 2009
Work from multiple groups continues to provide additional evidence for the powerful and highly diverse roles, both protective and pathogenic, that B cells play in autoimmune diseases. Similarly, it has become abundantly clear that antibody-independent functions may account for the opposing influences that B cells exercise over other arms of the immune response and ultimately over autoimmunity itself. Finally, it is becoming apparent that the clinical impact of B-cell depletion therapy may be, to a large extent, determined by the functional balance between different B-cell subsets that may be generated by this therapeutic intervention. In this review, we postulate that our perspective of B-cell tolerance and our experimental approach to its understanding are fundamentally changed by this view of B cells. Accordingly, we first discuss current knowledge of B-cell tolerance conventionally defined as the censoring of autoantibody-producing B cells (with an emphasis on human B cells). The...