Imbalanced PTEN and PI3K Signaling Impairs Class Switch Recombination.
J Immunol
; 195(11): 5461-5471, 2015 Dec 01.
Article
em En
| MEDLINE
| ID: mdl-26500350
ABSTRACT
Class switch recombination (CSR) generates isotype-switched Abs with distinct effector functions. B cells express phosphatase and tensin homolog (PTEN) and multiple isoforms of class IA PI3K catalytic subunits, including p110α and p110δ, whose roles in CSR remain unknown or controversial. In this article, we demonstrate a direct effect of PTEN on CSR signaling by acute deletion of Pten specifically in mature B cells, thereby excluding the developmental impact of Pten deletion. We show that mature B cell-specific PTEN overexpression enhances CSR. More importantly, we establish a critical role for p110α in CSR. Furthermore, we identify a cooperative role for p110α and p110δ in suppressing CSR. Mechanistically, dysregulation of p110α or PTEN inversely affects activation-induced deaminase expression via modulating AKT activity. Thus, our study reveals that a signaling balance between PTEN and PI3K isoforms is essential to maintain normal CSR.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Linfócitos B
/
Switching de Imunoglobulina
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PTEN Fosfo-Hidrolase
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Classe I de Fosfatidilinositol 3-Quinases
Limite:
Animals
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2015
Tipo de documento:
Article