Vav1 regulates MHCII expression in murine resting and activated B cells.
Int Immunol
; 25(5): 307-17, 2013 May.
Article
de En
| MEDLINE
| ID: mdl-23391492
ABSTRACT
Vav1 is a guanine nucleotide exchange factor (GEF) for Rho GTPases, which is exclusively expressed in cells of the hematopoietic system. In addition to its well-documented GEF activity, it was suggested to have other functions due to the presence of multiple domains and nuclear localization signals in its protein structure. Although GEF-dependent and GEF-independent functions of vav have been implicated in T-cell development and T-cell receptor signaling, the role of vav1 in antigen-presenting cells is poorly understood. We found that vav1 is an important regulator of MHCII expression and transport. Microarray analysis of unstimulated bone marrow-derived macrophages revealed a novel role of vav1 in transcriptional regulation of the MHCII locus, possibly by indirect means. Primary immune cells from vav1-deficient mice had a significantly lower constitutive surface expression of MHCII with the strongest impact observed on splenic and peritoneal B cells. Impaired MHCII expression resulted in a diminished capacity for T-cell activation. Using 6-thio-GTP, a specific inhibitor of the GEF function of vav1, we were able to show that the GEF activity is required for MHCII upregulation in B cells after stimulation with LPS. Furthermore, our data show that vav1 not only affects transcription of the MHCII locus but also is an important regulator of MHCII protein transport to the cell surface.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Lymphocytes B
/
Activation des lymphocytes
/
Antigènes d'histocompatibilité de classe II
/
Protéines proto-oncogènes c-vav
Limites:
Animals
Langue:
En
Journal:
Int Immunol
Sujet du journal:
ALERGIA E IMUNOLOGIA
Année:
2013
Type de document:
Article
Pays d'affiliation:
Allemagne