Development of peripheral lymphoid organs and natural killer cells depends on the helix-loop-helix inhibitor Id2

Nature. 1999 Feb 25;397(6721):702-6. doi: 10.1038/17812.


Transcription factors with a basic helix-loop-helix (HLH) motif have been shown to be crucial for various cell differentiation processes during development of multicellular organisms. Id proteins inhibit the functions of these transcription factors in a dominant-negative manner by suppressing their heterodimerization partners through the HLH domains. Members of the Id family also promote cell proliferation, implying a role in the control of cell differentiation. Here we show that Id2 is indispensable for normal development of mice. Id2-/- mice lack lymph nodes and Peyer's patches. However, their splenic architecture is normal, exhibiting T-cell and B-cell compartments and distinct germinal centres. The cell population that produces lymphotoxins, essential factors for the development of secondary lymphoid organs, is barely detectable in the Id2-/- intestine. Furthermore, the null mutants show a greatly reduced population of natural killer (NK) cells, which is due to an intrinsic defect in NK-cell precursors. Our results indicate that Id2 has an essential role in the generation of peripheral lymphoid organs and NK cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells
  • Bone Marrow Transplantation
  • Cell Division / physiology
  • Cell Line
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Embryonic and Fetal Development / physiology
  • Female
  • Gene Targeting
  • Helix-Loop-Helix Motifs*
  • Inhibitor of Differentiation Protein 2
  • Intestines / cytology
  • Intestines / embryology
  • Killer Cells, Natural / cytology*
  • Leukopoiesis / physiology*
  • Lymph Nodes / abnormalities
  • Lymph Nodes / cytology
  • Lymph Nodes / metabolism
  • Lymphocyte Subsets / cytology
  • Lymphocyte Subsets / immunology
  • Lymphocyte Subsets / metabolism
  • Lymphoid Tissue / abnormalities
  • Lymphoid Tissue / growth & development*
  • Lymphotoxin-alpha / biosynthesis
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Peyer's Patches / abnormalities
  • Repressor Proteins*
  • Spleen / abnormalities
  • Spleen / cytology
  • Stem Cells / cytology
  • Transcription Factors / antagonists & inhibitors


  • DNA-Binding Proteins
  • Idb2 protein, mouse
  • Inhibitor of Differentiation Protein 2
  • Lymphotoxin-alpha
  • Repressor Proteins
  • Transcription Factors