Abstract
Inositol 1,4,5-trisphosphate 3-kinase B (or Itpkb) converts inositol 1,4,5-trisphosphate to inositol 1,3,4,5-tetrakisphosphate upon Ag receptor activation and controls the fate and function of lymphocytes. To determine the role of Itpkb in B cell tolerance, Itpkb(-/-) mice were crossed to transgenic mice that express a BCR specific for hen egg lysozyme (IgHEL). B cells from Itpkb(-/-) IgHEL mice possess an anergic phenotype, hypoproliferate in response to cognate Ag, and yet they exhibit enhanced Ag-induced calcium signaling. In IgHEL transgenic mice that also express soluble HEL, lack of Itpkb converts anergy induction to deletion. These data establish Itpkb as a negative regulator of BCR signaling that controls the fate of developing B cells and tolerance induction.
MeSH terms
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Animals
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Apoptosis Regulatory Proteins / metabolism
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B-Lymphocytes / cytology
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B-Lymphocytes / drug effects
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B-Lymphocytes / enzymology*
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B-Lymphocytes / immunology*
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Bcl-2-Like Protein 11
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Bone Marrow / immunology
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Calcium / metabolism
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Cell Differentiation / immunology
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Cells, Cultured
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Gene Deletion
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Immune Tolerance / immunology*
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Inositol Phosphates / pharmacology
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Membrane Proteins / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Phosphotransferases (Alcohol Group Acceptor) / deficiency
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Phosphotransferases (Alcohol Group Acceptor) / genetics
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Phosphotransferases (Alcohol Group Acceptor) / metabolism*
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Protein Kinase Inhibitors / pharmacology
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Proto-Oncogene Proteins / metabolism
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Receptors, Antigen, B-Cell / immunology*
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Signal Transduction / immunology*
Substances
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Apoptosis Regulatory Proteins
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Bcl-2-Like Protein 11
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Bcl2l11 protein, mouse
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Inositol Phosphates
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Membrane Proteins
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Protein Kinase Inhibitors
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Proto-Oncogene Proteins
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Receptors, Antigen, B-Cell
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inositol-1,3,4,5-tetrakisphosphate
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Phosphotransferases (Alcohol Group Acceptor)
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Inositol 1,4,5-trisphosphate 3-kinase
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Calcium