Activating Receptor Signals Drive Receptor Diversity in Developing Natural Killer Cells.
PLoS Biol
; 14(8): e1002526, 2016 08.
Article
en En
| MEDLINE
| ID: mdl-27500644
ABSTRACT
It has recently been appreciated that NK cells exhibit many features reminiscent of adaptive immune cells. Considerable heterogeneity exists with respect to the ligand specificity of individual NK cells and as such, a subset of NK cells can respond, expand, and differentiate into memory-like cells in a ligand-specific manner. MHC I-binding inhibitory receptors, including those belonging to the Ly49 and KIR families, are expressed in a variegated manner, which creates ligand-specific diversity within the NK cell pool. However, how NK cells determine which inhibitory receptors to express on their cell surface during a narrow window of development is largely unknown. In this manuscript, we demonstrate that signals from activating receptors are critical for induction of Ly49 and KIR receptors during NK cell development; activating receptor-derived signals increased the probability of the Ly49 bidirectional Pro1 promoter to transcribe in the forward versus the reverse direction, leading to stable expression of Ly49 receptors in mature NK cells. Our data support a model where the balance of activating and inhibitory receptor signaling in NK cells selects for the induction of appropriate inhibitory receptors during development, which NK cells use to create a diverse pool of ligand-specific NK cells.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Células Asesinas Naturales
/
Transducción de Señal
/
Receptores KIR
/
Subfamilia A de Receptores Similares a Lectina de Células NK
Límite:
Animals
/
Humans
Idioma:
En
Revista:
PLoS Biol
Asunto de la revista:
BIOLOGIA
Año:
2016
Tipo del documento:
Article
País de afiliación:
Estados Unidos