A crucial role for the p110delta subunit of phosphatidylinositol 3-kinase in B cell development and activation

J Exp Med. 2002 Sep 16;196(6):753-63. doi: 10.1084/jem.20020805.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Isoenzymes
  • Phosphatidylinositol Phosphates
  • Protein Subunits
  • Proto-Oncogene Proteins
  • Receptors, Antigen, B-Cell
  • phosphatidylinositol 3,4,5-triphosphate
  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase
  • Btk protein, mouse
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Type C Phospholipases
  • Phospholipase C gamma
  • Calcium