Increased STAT3 phosphorylation on CD27(+) B-cells from common variable immunodeficiency disease patients.
Clin Immunol
; 161(2): 77-88, 2015 Dec.
Article
em En
| MEDLINE
| ID: mdl-26360251
ABSTRACT
Maturation and differentiation of B-cells are driven by T-cells' help through IL-21/STAT3 axis in GC centers or through extrafollicular pathways, in a T-independent manner. B-cell differentiation is defective in common variable immunodeficiency disease (CVID) patients. We investigated if IL-21/STAT3 axis alterations could influence B-cell fate. We activated purified CVID B-cells with surrogate T-dependent (anti-CD40), T-independent (TLR-9 ligand) stimuli or through B-cell receptor engagement (anti-IgM) with or without IL-21. IL-21 mediated STAT3 activation was greater on CD27(-) than CD27(+) B-cells depending on the stimulus. IL-21 alone induced STAT3 phosphorylation (pSTAT3) only on CD27(-) B-cells and IL-21 induced higher pSTAT3 levels on CD27(-) than CD27(+) B-cells after anti-IgM or anti-CD40 activation. CVID CD27(+) B-cells showed selective STAT3 hyperphosphorylation after activation with anti-IgM or anti-CD40 alone and anti-IgM, anti-CD40 or ODN combined with IL-21. Increased STAT3 activation during immune responses could result in B-cell differentiation defects in CVID.
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Base de dados:
MEDLINE
Assunto principal:
Fosforilação
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Linfócitos B
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Imunodeficiência de Variável Comum
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Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral
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Fator de Transcrição STAT3
Limite:
Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article