Journal
BLOOD
Volume 112, Issue 1, Pages 131-140Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2007-08-107847
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Funding
- NCI NIH HHS [R01 CA083859, R56 CA100226, CA100226, CA06927, P30 CA006927, CA083859, R01 CA100226] Funding Source: Medline
- NIAID NIH HHS [T32 AI007492, AI007492] Funding Source: Medline
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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 INK cells promotes functionality, terminal maturation, and long-term survival.
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