title: The BAFF receptor transduces survival signals by co-opting the B cell receptor signaling pathway.
abstract: 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.
authors: Division of Immune Cell Biology, MRC National Institute for Medical Research, London NW7 1AA, UK.
authors: Edina
authors: E
authors: Schweighoffer
authors: Lesley
authors: L
authors: Vanes
authors: Josquin
authors: J
authors: Nys
authors: Doreen
authors: D
authors: Cantrell
authors: Scott
authors: S
authors: McCleary
authors: Nicholas
authors: N
authors: Smithers
authors: Victor L J
authors: VL
authors: Tybulewicz
mesh_terms: D064413:3-Phosphoinositide-Dependent Protein Kinases; D000818:Animals; D053264:B-Cell Activating Factor / Q000276:immunology / Q000494:pharmacology; D053265:B-Cell Activation Factor Receptor / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051925:CD79 Antigens / Q000276:immunology / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D015151:Immunoblotting; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018448:Models, Immunological; D020411:Oligonucleotide Array Sequence Analysis; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D022661:RNA, Untranslated; D020239:Receptor Cross-Talk / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D000072377:Syk Kinase; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: D064413:3-Phosphoinositide-Dependent Protein Kinases; D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D051925:CD79 Antigens; D048049:Extracellular Signal-Regulated MAP Kinases; D047908:Intracellular Signaling Peptides and Proteins; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D011506:Proteins; D022661:RNA, Untranslated; D011947:Receptors, Antigen, B-Cell; D000072377:Syk Kinase; D013629:Tamoxifen; C110853:Gt(ROSA)26Sor non-coding RNA, mouse; C000606897:Syk protein, mouse