B cell-intrinsic signaling through IL-21 receptor and STAT3 is required for establishing long-lived antibody responses in humans.
J Exp Med
; 207(1): 155-71, 2010 Jan 18.
Article
em En
| MEDLINE
| ID: mdl-20048285
ABSTRACT
Engagement of cytokine receptors by specific ligands activate Janus kinase-signal transducer and activator of transcription (STAT) signaling pathways. The exact roles of STATs in human lymphocyte behavior remain incompletely defined. Interleukin (IL)-21 activates STAT1 and STAT3 and has emerged as a potent regulator of B cell differentiation. We have studied patients with inactivating mutations in STAT1 or STAT3 to dissect their contribution to B cell function in vivo and in response to IL-21 in vitro. STAT3 mutations dramatically reduced the number of functional, antigen (Ag)-specific memory B cells and abolished the ability of IL-21 to induce naive B cells to differentiate into plasma cells (PCs). This resulted from impaired activation of the molecular machinery required for PC generation. In contrast, STAT1 deficiency had no effect on memory B cell formation in vivo or IL-21-induced immunoglobulin secretion in vitro. Thus, STAT3 plays a critical role in generating effector B cells from naive precursors in humans. STAT3-activating cytokines such as IL-21 thus underpin Ag-specific humoral immune responses and provide a mechanism for the functional antibody deficit in STAT3-deficient patients.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Plasmócitos
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Transdução de Sinais
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Diferenciação Celular
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Interleucinas
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Fator de Transcrição STAT3
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Memória Imunológica
Limite:
Humans
Idioma:
En
Revista:
J Exp Med
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Austrália