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CXCR4 signaling and function require the expression of the IgD-class B-cell antigen receptor.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2017 May 16; Vol. 114 (20), pp. 5231-5236. Date of Electronic Publication: 2017 May 01. - Publication Year :
- 2017
-
Abstract
- Mature B cells coexpress both IgM and IgD B-cell antigen receptor (BCR) classes, which are organized on the cell surface in distinct protein islands. The specific role of the IgD-BCR is still enigmatic, but it is colocalized with several other receptors on the B-cell surface, including the coreceptor CD19. Here, we report that the chemokine receptor CXCR4 is also found in proximity to the IgD-BCR. Furthermore, B cells from IgD-deficient mice show defects in CXCL12-mediated CXCR4 signaling and B-cell migration, whereas B cells from IgM-deficient mice are normal in this respect. CXCR4 activation results in actin cytoskeleton remodeling and PI3K/Akt and Erk signaling in an IgD-BCR-dependent manner. The defects in CXCR4 signaling in IgD-deficient B cells can be overcome by anti-CD19 antibody stimulation that also increases CXCL12-mediated B-cell migration of normal B cells. These results show that the IgD-BCR, CD19, and CXCR4 are not only colocalized at nanometer distances but are also functionally connected, thus providing a unique paradigm of receptor signaling cross talk and function.<br />Competing Interests: The authors declare no conflict of interest.
- Subjects :
- Actin Cytoskeleton metabolism
Animals
Antigens, CD19 metabolism
B-Lymphocytes metabolism
Cytoskeleton metabolism
Immunoglobulin D immunology
Immunoglobulin M immunology
Immunoglobulin M metabolism
Mice
Mice, Inbred C57BL
Receptor Cross-Talk immunology
Receptors, CXCR4 immunology
Signal Transduction
Immunoglobulin D metabolism
Receptors, Antigen, B-Cell metabolism
Receptors, CXCR4 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 114
- Issue :
- 20
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 28461496
- Full Text :
- https://doi.org/10.1073/pnas.1621512114