IgG4 production is confined to human IL-10–producing regulatory B cells that suppress antigen-specific immune responses - 30/03/13
Corresponding author: Mübeccel Akdis, MD, PhD, Swiss Institute of Allergy and Asthma Research (SIAF), Obere Strasse 22, CH-7270, Davos, Switzerland.Abstract |
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. IgG4 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-10–secreting B regulatory 1 (BR1) 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 A2 (PLA) were isolated from beekeepers who displayed tolerance to bee venom antigens and allergic patients before and after specific immunotherapy.
Results |
Human IL-10+ BR1 cells expressed high surface CD25 and CD71 and low CD73 levels. Sorting of CD73−CD25+CD71+ B cells allowed enrichment of human BR1 cells, which produced high levels of IL-10 and potently suppressed antigen-specific CD4+ T-cell proliferation. IgG4 was selectively confined to human BR1 cells. B cells specific for the major bee venom allergen PLA isolated from nonallergic beekeepers show increased expression of IL-10 and IgG4. Furthermore, the frequency of IL-10+ PLA-specific B cells increased in allergic patients receiving allergen-specific immunotherapy.
Conclusion |
Our data show the characterization of IL-10+ BR1 cells and in vivo evidence for 2 essential features of allergen tolerance: the suppressive B cells and IgG4-expressing B cells that are confined to IL-10+ BR1 cells in human subjects.
Le texte complet de cet article est disponible en PDF.Key words : Immune tolerance, regulatory B cells, IL-10, IgG4
Abbreviations used : BR1, Breg, IL-10R, PLA, PPD, SIT, TLR, TLR9-L, TR1, Treg
Plan
| Supported by Swiss National Science Foundation (grant nos. 320030-125249/1, 32-188226, and 320030-140772), the Christine Kühne-Center for Allergy Research and Education (CK-CARE), and the European Commission’s Seventh Framework Programme (grant agreement no. 261357 [MEDALL]). |
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| Disclosure of potential conflict of interest: C. A. Akdis has received one or more consulting fees or honoraria from Actellion, Aventis, Stallergenes, Allergopharma, and Circacia; is employed by the Swiss Institute of Allergy and Asthma Research, University of Zurich, Zurich, Switzerland; and has received one or more grants from or has one or more grants pending with Novartis Research on immunoregulation in asthma (PREDICTA: European Commission’s Seventh Framework programme No. 260895, Research on virus induced exacerbations; Swiss National Science Foundation Research on T cell interaction with the epithelium; MeDALL: European Commission’s Seventh Framework; Programme No. 261357, Research on early initiation of asthma) and the Christine Kühne-Center for Allergy Research and Education Research on severe allergies. M. Akdis has been supported by one or more grants from the Swiss National Science Foundation (EU 7FW project, Predicta, MeDALL). The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 131 - N° 4
P. 1204-1212 - avril 2013 Retour au numéro
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