Dock5 controls the peripheral B cell differentiation via regulating BCR signaling and actin reorganization.
Cell Immunol
; 337: 15-21, 2019 03.
Article
em En
| MEDLINE
| ID: mdl-30661670
ABSTRACT
As an atypical guanine nucleotide exchange factor (GEF), Dock5 has been extensively studied in cellular functions. However, the role of Dock5 on B-cell immunity still remain elusive. In this study, we generated a Dock5 knockout mouse model to study the effect of Dock5 deficiency on B cell development, differentiation and BCR signaling. We found that the absence of Dock5 leads to a moderate effect on B cell development in the bone marrow and reduces follicular (FO) and marginal zone (MZ) B cells. Mechanistically, the key positive upstream B-cell receptor (BCR) signaling molecules, CD19 and Brutons tyrosine kinase (Btk), whose activation determines the fate of FO and MZ B cells, is reduced in Dock5 KO B cells upon antigenic stimulation by using total internal reflection fluorscence microscopy (TIRF) and immunoblot. Interestingly we found that the cellular filamentous actin (F-actin), also decreased in Dock5 KO B cells upon stimulation, which, in turn, offers feedback to BCR signaling. Our study has unveiled that Dock5 regulates the peripheral B cell differentiation via controlling the CD19-Btk signaling axis as well as actin reorganization.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos B
/
Receptores de Antígenos de Linfócitos B
/
Fatores de Troca do Nucleotídeo Guanina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Cell Immunol
Ano de publicação:
2019
Tipo de documento:
Article