The BAFF Receptor Transduces Survival Signals by Co-opting the B Cell Receptor Signaling Pathway
The BAFF Receptor Transduces Survival Signals by Co-opting the B Cell Receptor Signaling Pathway
Follicular B cell survival requires signaling from BAFFR, a receptor for BAFF and the B cell antigen receptor (BCR). This "tonic" BCR survival signal is distinct from that induced by antigen binding and may be ligand-independent. We show that inducible inactivation of the Syk tyrosine kinase, a key signal transducer from the BCR following antigen binding, resulted in the death of most follicular B cells because Syk-deficient cells were unable to survive in response to BAFF. Genetic rescue studies demonstrated that Syk transduces BAFFR survival signals via ERK and PI3 kinase. Surprisingly, BAFFR signaling directly induced phosphorylation of both Syk and the BCR-associated Igα signaling subunit, and this Syk phosphorylation required the BCR. We conclude that the BCR and Igα may be required for B cell survival because they function as adaptor proteins in a BAFFR signaling pathway leading to activation of Syk, demonstrating previously unrecognized crosstalk between the two receptors.
- University of Dundee United Kingdom
- Cellzome, GSK, Middlesex, UK.
- National Institute for Medical Research United Kingdom
Cell Survival, Immunology, Immunoblotting, 610, Mice, Transgenic, Protein Serine-Threonine Kinases, Article, 3-Phosphoinositide-Dependent Protein Kinases, Mice, Phosphatidylinositol 3-Kinases, /dk/atira/pure/subjectarea/asjc/2700/2723, B-Cell Activating Factor, /dk/atira/pure/subjectarea/asjc/2700/2725, Immunology and Allergy, Animals, name=Immunology, /dk/atira/pure/subjectarea/asjc/2400/2403, Phosphorylation, Extracellular Signal-Regulated MAP Kinases, Oligonucleotide Array Sequence Analysis, Mice, Knockout, B-Lymphocytes, Gene Expression Profiling, Intracellular Signaling Peptides and Proteins, Models, Immunological, Flow Cytometry, name=Infectious Diseases, name=Immunology and Allergy, Infectious Diseases, CD79 Antigens, B-Cell Activation Factor Receptor
Cell Survival, Immunology, Immunoblotting, 610, Mice, Transgenic, Protein Serine-Threonine Kinases, Article, 3-Phosphoinositide-Dependent Protein Kinases, Mice, Phosphatidylinositol 3-Kinases, /dk/atira/pure/subjectarea/asjc/2700/2723, B-Cell Activating Factor, /dk/atira/pure/subjectarea/asjc/2700/2725, Immunology and Allergy, Animals, name=Immunology, /dk/atira/pure/subjectarea/asjc/2400/2403, Phosphorylation, Extracellular Signal-Regulated MAP Kinases, Oligonucleotide Array Sequence Analysis, Mice, Knockout, B-Lymphocytes, Gene Expression Profiling, Intracellular Signaling Peptides and Proteins, Models, Immunological, Flow Cytometry, name=Infectious Diseases, name=Immunology and Allergy, Infectious Diseases, CD79 Antigens, B-Cell Activation Factor Receptor
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