Human regulatory B cells combine phenotypic and genetic hallmarks with a distinct differentiation fate.
J Immunol
; 193(5): 2258-66, 2014 Sep 01.
Article
em En
| MEDLINE
| ID: mdl-25080484
ABSTRACT
Regulatory B cells (B-reg) produce IL-10 and suppress inflammation in both mice and humans, but limited data on the phenotype and function of these cells have precluded detailed assessment of their contribution to host immunity. In this article, we report that human B-reg cannot be defined based on a phenotype composed of conventional B cell markers, and that IL-10 production can be elicited in both the CD27(+) memory population and naive B cell subset after only a brief stimulation in vitro. We therefore sought to obtain a better definition of IL-10-producing human B-regs using a multiparameter analysis of B cell phenotype, function, and gene expression profile. Exposure to CpG and anti-Ig are the most potent stimuli for IL-10 secretion in human B cells, but microarray analysis revealed that human B cells cotreated with these reagents resulted in only â¼0.7% of genes being differentially expressed between IL-10(+) and IL-10(-) cells. Instead, connectivity map analysis revealed that IL-10-secreting B cells are those undergoing specific differentiation toward a germinal center fate, and we identified a CD11c(+) B cell subset that was not capable of producing IL-10 even under optimal conditions. Our findings will assist in the identification of a broader range of human pro-B-reg populations that may represent novel targets for immunotherapy.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Diferenciação Celular
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Subpopulações de Linfócitos B
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Interleucina-10
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article