Impact of β2 integrin deficiency on mouse natural killer cell development and function

Blood. 2011 Mar 10;117(10):2874-82. doi: 10.1182/blood-2010-10-315457. Epub 2011 Jan 14.


Natural killer (NK) cells are innate immune cells that express members of the leukocyte β2 integrin family in humans and mice. These CD11/CD18 heterodimers play critical roles in leukocyte trafficking, immune synapse formation, and costimulation. The cell-surface expression of one of these integrins, CD11b/CD18, is also recognized as a major marker of mouse NK-cell maturation, but its function on NK cells has been largely ignored. Using N-ethyl-N-nitrosourea (ENU) mutagenesis, we generated a mouse carrying an A → T transverse mutation in the Itgb2 gene, resulting in a mutation that prevented the cell-surface expression of CD18 and its associated CD11a, CD11b, and CD11c proteins. We show that β2 integrin-deficient NK cells have a hyporesponsive phenotype in vitro, and present an alteration of their in vivo developmental program characterized by a selective accumulation of c-kit(+) cells. NK-cell missing-self recognition was partially altered in vivo, whereas the early immune response to mouse cytomegalovirus (MCMV) infection occurred normally in CD18-deficient mice. Therefore, β2 integrins are required for optimal NK-cell maturation, but this deficiency is partial and can be bypassed during MCMV infection, highlighting the robustness of antiviral protective responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD18 Antigens / immunology*
  • CD18 Antigens / metabolism*
  • Cell Differentiation / immunology*
  • Cell Separation
  • Flow Cytometry
  • Herpesviridae Infections / immunology
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / immunology*
  • Mice
  • Muromegalovirus / immunology


  • CD18 Antigens