Requirement for Rictor in homeostasis and function of mature B lymphoid cells.
Blood
; 122(14): 2369-79, 2013 Oct 03.
Article
em En
| MEDLINE
| ID: mdl-23958952
ABSTRACT
The mammalian target of rapamycin (mTOR), an essential serine/threonine kinase, functions in biochemically distinct multiprotein complexes, but little is known about roles of the complexes in B cells. The acutely rapamycin-sensitive mTOR complex 1 (mTORC1) is defined by a core subunit Raptor, whereas mTORC2 lacks Raptor and, instead, has Rictor and SIN1 as distinct essential components. We now show that homeostasis and function of B cells require Rictor. Conditional deletion of Rictor before lymphoid specification impaired generation of mature follicular, marginal zone, and B1a B lymphocytes. Induced inactivation in adult mice caused cell-autonomous defects in B lymphoid homeostasis and antibody responses in vivo, along with affecting plasma cells in bone marrow. Survival of B lymphocytes depended on Rictor, which was vital for normal induction of prosurvival genes, suppression of proapoptotic genes, nuclear factor κB induction after B-cell receptor stimulation, and B-cell activating factor-induced nuclear factor κB2/p52 generation. Collectively, the findings provide evidence that mTOR signaling affects survival and proliferation of mature B lymphocytes, and establish Rictor as an important signal relay in B-cell homeostasis, fate, and functions.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos B
/
Proteínas de Transporte
/
Diferenciação Celular
/
Homeostase
Limite:
Animals
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article