A distinct subpopulation of human NK cells restricts B cell transformation by EBV

J Immunol. 2013 Nov 15;191(10):4989-95. doi: 10.4049/jimmunol.1301046. Epub 2013 Oct 9.


NK cells constitute the first line of defense against pathogens and transformed cells. They mature in secondary lymphoid organs, including tonsils, where common pathogens, such as EBV, enter the host and potentially imprint differentiating cells, which then patrol the body via the blood stream. Therefore, we set out to characterize a distinct human NK cell population in tonsils that produces high amounts of the immunomodulatory and antiviral cytokine IFN-γ. We found that the tonsilar IFN-γ(high) NK cell subset is CD56(bright)NKG2A(+)CD94(+)CD54(+)CD62L(-), is present in tonsils ex vivo and is more mature than other CD56(bright) NK cells in tonsils and less mature than other NK cells in blood, shows very low plasticity even after prolonged cytokine stimulation, accumulates in tonsils of EBV carriers, and is able to potently restrict EBV-induced transformation of B cells. Thus, we characterized a distinct and stable IFN-γ(high) NK cell subpopulation that can specifically restrict malignant transformation of EBV-infected B cells. This subset should be exploited for future development of cell-based therapeutic approaches in EBV-associated malignancies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / immunology*
  • B-Lymphocytes / virology*
  • CD56 Antigen / metabolism
  • Epstein-Barr Virus Infections / immunology*
  • Herpesvirus 4, Human / immunology
  • Humans
  • Intercellular Adhesion Molecule-1 / metabolism
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / metabolism
  • Killer Cells, Natural / immunology*
  • L-Selectin / metabolism
  • Lymphocyte Activation / immunology*
  • NK Cell Lectin-Like Receptor Subfamily C / metabolism
  • NK Cell Lectin-Like Receptor Subfamily D / metabolism
  • Palatine Tonsil / cytology
  • Palatine Tonsil / immunology


  • CD56 Antigen
  • NK Cell Lectin-Like Receptor Subfamily C
  • NK Cell Lectin-Like Receptor Subfamily D
  • Intercellular Adhesion Molecule-1
  • L-Selectin
  • Interferon-gamma