Enhanced NK-cell development and function in BCAP-deficient mice

Blood. 2008 Jul 1;112(1):131-40. doi: 10.1182/blood-2007-08-107847. Epub 2008 Mar 12.


In B lymphocytes, the B-cell adaptor for phosphatidylinositol 3-kinase (BCAP) facilitates signaling from the antigen receptor. Mice lacking BCAP have a predominantly immature pool of B cells with impaired immune function and increased susceptibility to apoptosis. Unexpectedly, we have found that natural killer (NK) cells from BCAP-deficient mice are more mature, more long-lived, more resistant to apoptosis, and exhibit enhanced functional activity compared with NK cells from wild-type mice. Surprisingly, these effects are evident despite a severe impairment of the immunoreceptor tyrosine-based activation motif-mediated Akt signaling pathway. The seemingly paradoxical phenotype reveals inherent differences in the signals controlling the final maturation of B cells and NK cells, which depend on positive and negative signals, respectively. Both enhanced interferon-gamma responses and augmented maturation of NK cells in BCAP-deficient mice are independent of available MHC class I ligands. Our data support a model in which blunting of BCAP-mediated activation signaling in developing NK cells promotes functionality, terminal maturation, and long-term survival.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / deficiency*
  • Adaptor Proteins, Signal Transducing / genetics
  • Animals
  • Apoptosis
  • Cell Differentiation
  • Cellular Senescence
  • Cytotoxicity, Immunologic
  • Female
  • Humans
  • Interferon-gamma / biosynthesis
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism*
  • Male
  • Mice
  • Mice, Congenic
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Immunological
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Self Tolerance
  • Signal Transduction


  • Adaptor Proteins, Signal Transducing
  • Pik3ap1 protein, mouse
  • Interferon-gamma
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt