title: CD19 and BAFF-R can signal to promote B-cell survival in the absence of Syk.
abstract: The development and function of B lymphocytes is regulated by numerous signaling pathways, some emanating from the B-cell antigen receptor (BCR). The spleen tyrosine kinase (Syk) plays a central role in the activation of the BCR, but less is known about its contribution to the survival and maintenance of mature B cells. We generated mice with an inducible and B-cell-specific deletion of the Syk gene and found that a considerable fraction of mature Syk-negative B cells can survive in the periphery for an extended time. Syk-negative B cells are defective in BCR, RP105 and CD38 signaling but still respond to an IL-4, anti-CD40, CpG or LPS stimulus. Our in vivo experiments show that Syk-deficient B cells require BAFF receptor and CD19/PI3K signaling for their long-term survival. These studies also shed a new light on the signals regulating the maintenance of the normal mature murine B-cell pool.
authors: Max-Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany Department of Molecular Immunology, BioIII, Faculty of Biology, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany hobeika@ie-freiburg.mpg.de michael.reth@bioss.uni-freiburg.de.
authors: Elias
authors: E
authors: Hobeika
authors: Max-Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
authors: Ella
authors: E
authors: Levit-Zerdoun
authors: Institute of Immunology, Charité Campus Buch, Berlin, Germany.
authors: Vasiliki
authors: V
authors: Anastasopoulou
authors: Max-Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
authors: Roland
authors: R
authors: Pohlmeyer
authors: Institute of Mircobiology, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland.
authors: Simon
authors: S
authors: Altmeier
authors: Department of General Pediatrics, University Medical Center Schleswig-Holstein, Kiel, Germany.
authors: Ameera
authors: A
authors: Alsadeq
authors: Laboratory of Immune Cell Epigenetics and Signaling, The Rockefeller University, New York, NY, USA.
authors: Marc-Werner
authors: MW
authors: Dobenecker
authors: Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, USA.
authors: Roberta
authors: R
authors: Pelanda
authors: Max-Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany Department of Molecular Immunology, BioIII, Faculty of Biology, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany BIOSS, Centre For Biological Signaling Studies, University of Freiburg, Freiburg, Germany hobeika@ie-freiburg.mpg.de michael.reth@bioss.uni-freiburg.de.
authors: Michael
authors: M
authors: Reth
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000235:genetics / Q000276:immunology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D018941:Antigens, CD19 / Q000235:genetics / Q000276:immunology*; D053265:B-Cell Activation Factor Receptor / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D019013:CD40 Antigens / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000276:immunology*; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D000072377:Syk Kinase
chemical_list: D000906:Antibodies; D015703:Antigens, CD; D018941:Antigens, CD19; D053265:B-Cell Activation Factor Receptor; D019013:CD40 Antigens; C408982:CPG-oligonucleotide; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; C490500:Ly78 protein, mouse; D008562:Membrane Glycoproteins; D009838:Oligodeoxyribonucleotides; D011947:Receptors, Antigen, B-Cell; C486662:Tnfrsf13c protein, mouse; D015847:Interleukin-4; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse; C498155:Cd38 protein, mouse; D051997:ADP-ribosyl Cyclase 1
keywords: BAFF receptor; B‐cell antigen receptor; CD19; Syk; mb1‐CreERT2
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