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Dock5 controls the peripheral B cell differentiation via regulating BCR signaling and actin reorganization.
- Source :
-
Cellular immunology [Cell Immunol] 2019 Mar; Vol. 337, pp. 15-21. Date of Electronic Publication: 2019 Jan 11. - Publication Year :
- 2019
-
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.<br /> (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Subjects :
- Actins metabolism
Adaptor Proteins, Signal Transducing immunology
Animals
Antigens, CD19
B-Lymphocytes immunology
Cell Differentiation
Guanine Nucleotide Exchange Factors immunology
Lymphocyte Activation immunology
Mice
Mice, Inbred C57BL
Mice, Knockout
Protein-Tyrosine Kinases metabolism
Signal Transduction immunology
B-Lymphocytes metabolism
Guanine Nucleotide Exchange Factors metabolism
Receptors, Antigen, B-Cell metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2163
- Volume :
- 337
- Database :
- MEDLINE
- Journal :
- Cellular immunology
- Publication Type :
- Academic Journal
- Accession number :
- 30661670
- Full Text :
- https://doi.org/10.1016/j.cellimm.2019.01.001