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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.

Type

Journal article

Journal

J Exp Med

Publication Date

16/09/2002

Volume

196

Pages

753 - 763

Keywords

Agammaglobulinaemia Tyrosine Kinase, Animals, Antibody Formation, B-Lymphocytes, Calcium, Isoenzymes, Lymphocyte Activation, Male, Mice, Mice, Knockout, Phosphatidylinositol 3-Kinases, Phosphatidylinositol Phosphates, Phospholipase C gamma, Protein Subunits, Protein-Serine-Threonine Kinases, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-akt, Receptors, Antigen, B-Cell, Type C Phospholipases