| First Author | MacFarlane AW 4th | Year | 2008 |
| Journal | Blood | Volume | 112 |
| Issue | 1 | Pages | 131-40 |
| PubMed ID | 18337558 | Mgi Jnum | J:137306 |
| Mgi Id | MGI:3798742 | Doi | 10.1182/blood-2007-08-107847 |
| Citation | MacFarlane AW 4th, et al. (2008) Enhanced NK-cell development and function in BCAP-deficient mice. Blood 112(1):131-40 |
| abstractText | 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. |
