Abstract
Mice lacking the p110delta catalytic subunit of phosphatidylinositol 3-kinase have reduced numbers of B1 and marginal zone B cells, reduced levels of serum immunoglobulins, respond poorly to immunization with type II thymus-independent antigen, and are defective in their primary and secondary responses to thymus-dependent antigen. p110delta(-/-) B cells proliferate poorly in response to B cell receptor (BCR) or CD40 signals in vitro, fail to activate protein kinase B, and are prone to apoptosis. p110delta function is required for BCR-mediated calcium flux, activation of phosphlipaseCgamma2, and Bruton's tyrosine kinase. Thus, p110delta plays a critical role in B cell homeostasis and function.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Agammaglobulinaemia Tyrosine Kinase
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Animals
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Antibody Formation
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B-Lymphocytes / physiology*
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Calcium / metabolism
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Isoenzymes / physiology
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Lymphocyte Activation*
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Male
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Mice
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Mice, Knockout
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Phosphatidylinositol 3-Kinases / physiology*
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Phosphatidylinositol Phosphates / biosynthesis
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Phospholipase C gamma
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Protein Serine-Threonine Kinases*
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Protein Subunits
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Protein-Tyrosine Kinases / physiology
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Proto-Oncogene Proteins / physiology
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Proto-Oncogene Proteins c-akt
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Receptors, Antigen, B-Cell / physiology
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Type C Phospholipases / physiology
Substances
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Isoenzymes
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Phosphatidylinositol Phosphates
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Protein Subunits
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Proto-Oncogene Proteins
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Receptors, Antigen, B-Cell
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phosphatidylinositol 3,4,5-triphosphate
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Protein-Tyrosine Kinases
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Agammaglobulinaemia Tyrosine Kinase
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Btk protein, mouse
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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Type C Phospholipases
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Phospholipase C gamma
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Calcium