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CX3CR1 positively regulates BCR signaling coupled with cell metabolism via negatively controlling actin remodeling
- Source :
- Cellular and Molecular Life Sciences. 77:4379-4395
- Publication Year :
- 2020
- Publisher :
- Springer Science and Business Media LLC, 2020.
-
Abstract
- As an important chemokine receptor, the role of CX3CR1 has been studied extensively on the migration of lymphocytes including T and B cells. Although CX3CR1+ B cells have immune suppressor properties, little is known about its role on the regulation of BCR signaling and B cell differentiation as well as the underlying molecular mechanism. We have used CX3CR1 KO mice to study the effect of CX3CR1 deficiency on BCR signaling and B cell differentiation. Interestingly, we found that proximal BCR signaling, such as the activation of CD19, BTK and SHIP was reduced in CX3CR1 KO B cells upon antigenic stimulation. However, the activation of mTORC signaling was enhanced. Mechanistically, we found that the reduced BCR signaling in CX3CR1 KO B cells was due to reduced BCR clustering, which is caused by the enhanced actin accumulation by the plasma membrane via increased activation of WASP. This caused an increased differentiation of MZ B cells in CX3CR1 KO mice and an enhanced generation of plasma cells (PC) and antibodies. Our study shows that CX3CR1 regulates BCR signaling via actin remodeling and affects B cell differentiation and the humoral immune response.
- Subjects :
- CX3C Chemokine Receptor 1
Receptors, Antigen, B-Cell
CD19
03 medical and health sciences
Cellular and Molecular Neuroscience
Chemokine receptor
Immune system
hemic and lymphatic diseases
medicine
Animals
Bruton's tyrosine kinase
Molecular Biology
B cell
Mice, Knockout
Pharmacology
B-Lymphocytes
0303 health sciences
biology
Chemistry
030302 biochemistry & molecular biology
breakpoint cluster region
Actin remodeling
Cell Differentiation
Cell Biology
Actins
Cell biology
Mice, Inbred C57BL
medicine.anatomical_structure
biology.protein
Molecular Medicine
Antibody
Signal Transduction
Subjects
Details
- ISSN :
- 14209071 and 1420682X
- Volume :
- 77
- Database :
- OpenAIRE
- Journal :
- Cellular and Molecular Life Sciences
- Accession number :
- edsair.doi.dedup.....2324dec0327a5020ece86c850b90efb1