NF-kappa B p50/p65 affects the frequency of Ly49 gene expression by NK cells

J Immunol. 2007 Aug 1;179(3):1751-9. doi: 10.4049/jimmunol.179.3.1751.


In mice, acquisition of Ly49 receptors characterizes one of the developmental stages of NK cells. We previously described a novel Ly49 promoter, Pro1, involved in Ly49 gene regulation in immature NK cells. Pro1 transcriptional activity requires a NF-kappaB binding site; however, only NF-kappaB/p50 binding to this element was observed. Cotransfection of NF-kappaB/p65 with Ly49g Pro1 in LNK cells induced a decrease in the transcriptional activity of the core promoter. Moreover, decreasing NF-kappaB/p65 protein expression by RNA interference increases Pro1 transcriptional activity. A high rate of NF-kappaB/p65 degradation in LNK cells correlates with Pro1 activity, since treatment with the proteasome inhibitor MG132 increased levels of NF-kappaB/p65 protein and decreased Pro1 activity. In addition, analysis of the Ly49 repertoire in NF-kappaB/p50 null mice reveals a decrease in the proportion of NK cells expressing a given Ly49 molecule. The defect in Ly49 expression is observed in the bone marrow and the spleen with a similar altered pattern of developmental stages in each tissue. The frequency of Ly49 expression in NF-kappaB/p52 null mice is slightly increased, indicating the specific role of NF-kappaB/p50 in Ly49 gene activation. These results suggest that NF-kappaB p50/p65 plays a major role in the initiation of Ly49 gene expression in NK cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Antigens, Ly / biosynthesis*
  • Antigens, Ly / genetics*
  • Cell Aggregation / genetics
  • Cell Aggregation / immunology
  • Cell Line
  • Cell Line, Tumor
  • Cytotoxicity, Immunologic / genetics
  • Down-Regulation / genetics
  • Down-Regulation / immunology
  • Gene Expression Regulation / immunology*
  • Gene Frequency / immunology*
  • Interferon-gamma / biosynthesis
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism*
  • Lectins, C-Type / antagonists & inhibitors
  • Lectins, C-Type / biosynthesis*
  • Lectins, C-Type / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NF-kappa B p50 Subunit / deficiency
  • NF-kappa B p50 Subunit / genetics
  • NF-kappa B p50 Subunit / physiology*
  • NF-kappa B p52 Subunit / biosynthesis
  • NF-kappa B p52 Subunit / genetics
  • NK Cell Lectin-Like Receptor Subfamily A
  • Promoter Regions, Genetic / immunology
  • Receptors, NK Cell Lectin-Like
  • Transcription Factor RelA / physiology*
  • Transcriptional Activation / immunology


  • Antigens, Ly
  • Klra7 protein, mouse
  • Lectins, C-Type
  • NF-kappa B p50 Subunit
  • NF-kappa B p52 Subunit
  • NK Cell Lectin-Like Receptor Subfamily A
  • Receptors, NK Cell Lectin-Like
  • Rela protein, mouse
  • Transcription Factor RelA
  • Nfkb1 protein, mouse
  • Interferon-gamma