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The mouse NKR-P1B:Clr-b recognition system is a negative regulator of innate immune responses.
- Source :
-
Blood [Blood] 2015 Apr 02; Vol. 125 (14), pp. 2217-27. Date of Electronic Publication: 2015 Jan 22. - Publication Year :
- 2015
-
Abstract
- NKR-P1B is a homodimeric type II transmembrane C-type lectinlike receptor that inhibits natural killer (NK) cell function upon interaction with its cognate C-type lectin-related ligand, Clr-b. The NKR-P1B:Clr-b interaction represents a major histocompatibility complex class I (MHC-I)-independent missing-self recognition system that monitors cellular Clr-b levels. We have generated NKR-P1B(B6)-deficient (Nkrp1b(-/-)) mice to study the role of NKR-P1B in NK cell development and function in vivo. NK cell inhibition by Clr-b is abolished in Nkrp1b(-/-) mice, confirming the inhibitory nature of NKR-P1B(B6). Inhibitory receptors also promote NK cell tolerance and responsiveness to stimulation; hence, NK cells expressing NKR-P1B(B6) and Ly49C/I display augmented responsiveness to activating signals vs NK cells expressing either or none of the receptors. In addition, Nkrp1b(-/-) mice are defective in rejecting cells lacking Clr-b, supporting a role for NKR-P1B(B6) in MHC-I-independent missing-self recognition of Clr-b in vivo. In contrast, MHC-I-dependent missing-self recognition is preserved in Nkrp1b(-/-) mice. Interestingly, spontaneous myc-induced B lymphoma cells may selectively use NKR-P1B:Clr-b interactions to escape immune surveillance by wild-type, but not Nkrp1b(-/-), NK cells. These data provide direct genetic evidence of a role for NKR-P1B in NK cell tolerance and MHC-I-independent missing-self recognition.<br /> (© 2015 by The American Society of Hematology.)
- Subjects :
- Animals
Blotting, Western
Cells, Cultured
Female
Flow Cytometry
Histocompatibility Antigens Class I immunology
Histocompatibility Antigens Class I metabolism
Ligands
Lymphoma, B-Cell metabolism
Lymphoma, B-Cell pathology
Male
Mice
Mice, Inbred C57BL
Immunity, Innate immunology
Killer Cells, Natural immunology
Lectins, C-Type physiology
Lymphoma, B-Cell immunology
Membrane Proteins physiology
NK Cell Lectin-Like Receptor Subfamily B physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 125
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 25612621
- Full Text :
- https://doi.org/10.1182/blood-2014-02-556142