IgG4 production is confined to human IL-10-producing regulatory B cells that suppress antigen-specific immune responses.
J Allergy Clin Immunol
; 131(4): 1204-12, 2013 Apr.
Article
en En
| MEDLINE
| ID: mdl-23453135
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Venenos de Abeja
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Inmunoglobulina G
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Interleucina-10
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Linfocitos B Reguladores
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Tolerancia Periférica
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Hipersensibilidad Inmediata
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Antígenos
Tipo de estudio:
Prognostic_studies
Límite:
Adolescent
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Adult
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Aged
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Humans
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Middle aged
Idioma:
En
Revista:
J Allergy Clin Immunol
Año:
2013
Tipo del documento:
Article
País de afiliación:
Suiza