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.
Keywords:
BAFF receptor; B‐cell antigen receptor; CD19; Syk; mb1‐CreERT2.
© 2015 The Authors.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ADP-ribosyl Cyclase 1 / genetics
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ADP-ribosyl Cyclase 1 / immunology
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Animals
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Antibodies / pharmacology
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Antigens, CD / genetics
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Antigens, CD / immunology
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Antigens, CD19 / genetics
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Antigens, CD19 / immunology*
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B-Cell Activation Factor Receptor / genetics
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B-Cell Activation Factor Receptor / immunology
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B-Lymphocytes / cytology
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B-Lymphocytes / immunology*
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CD40 Antigens / antagonists & inhibitors
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CD40 Antigens / genetics
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CD40 Antigens / immunology
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Cell Survival / genetics
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Cell Survival / immunology
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Interleukin-4 / antagonists & inhibitors
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Interleukin-4 / genetics
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Interleukin-4 / immunology
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / immunology*
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Lipopolysaccharides / pharmacology
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / immunology
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Mice
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Mice, Knockout
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Oligodeoxyribonucleotides / pharmacology
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Phosphatidylinositol 3-Kinases / genetics
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Phosphatidylinositol 3-Kinases / immunology
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Protein-Tyrosine Kinases / genetics
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Protein-Tyrosine Kinases / immunology*
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Receptors, Antigen, B-Cell / genetics
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Receptors, Antigen, B-Cell / immunology
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Signal Transduction / genetics
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Signal Transduction / immunology*
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Syk Kinase
Substances
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Antibodies
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Antigens, CD
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Antigens, CD19
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B-Cell Activation Factor Receptor
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CD40 Antigens
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CPG-oligonucleotide
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Intracellular Signaling Peptides and Proteins
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Lipopolysaccharides
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Ly78 protein, mouse
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Membrane Glycoproteins
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Oligodeoxyribonucleotides
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Receptors, Antigen, B-Cell
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Tnfrsf13c protein, mouse
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Interleukin-4
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Phosphatidylinositol 3-Kinases
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Protein-Tyrosine Kinases
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Syk Kinase
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Syk protein, mouse
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Cd38 protein, mouse
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ADP-ribosyl Cyclase 1