The mouse NKR-P1B:Clr-b recognition system is a negative regulator of innate immune responses

Blood. 2015 Apr 2;125(14):2217-27. doi: 10.1182/blood-2014-02-556142. Epub 2015 Jan 22.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cells, Cultured
  • Female
  • Flow Cytometry
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class I / metabolism
  • Immunity, Innate / immunology*
  • Killer Cells, Natural / immunology*
  • Lectins, C-Type / physiology*
  • Ligands
  • Lymphoma, B-Cell / immunology*
  • Lymphoma, B-Cell / metabolism
  • Lymphoma, B-Cell / pathology
  • Male
  • Membrane Proteins / physiology*
  • Mice
  • Mice, Inbred C57BL
  • NK Cell Lectin-Like Receptor Subfamily B / physiology*


  • Histocompatibility Antigens Class I
  • Klrb1b protein, mouse
  • Lectins, C-Type
  • Ligands
  • Membrane Proteins
  • NK Cell Lectin-Like Receptor Subfamily B
  • Ocil protein, mouse