B cell growth is controlled by phosphatidylinosotol 3-kinase-dependent induction of Rel/NF-kappaB regulated c-myc transcription

Mol Cell. 2002 Dec;10(6):1283-94. doi: 10.1016/s1097-2765(02)00779-7.


Rel/NF-kappaB transcription factors regulate the division and survival of B lymphocytes. Here we show that B cells lacking NF-kappaB1 and c-Rel fail to increase in size upon mitogenic stimulation due to a reduction in induced c-myc expression. Mitogen-induced B cell growth, although not markedly impaired by FRAP/mTOR or MEK inhibitors, required phosphatidylinositol 3-kinase (PI3K) activity. Inhibition of PI3K-dependent growth coincided with a block in the nuclear import of NF-kappaB1/c-Rel dimers and a failure to upregulate c-myc. In addition, PI3K was shown to be necessary for a transcription-independent increase in c-Myc protein levels that accompanies mitogenic activation. Collectively, these findings establish a role for Rel/NF-kappaB signaling in the mitogen-induced growth of mammalian cells, which in B lymphocytes requires a PI3K/c-myc-dependent pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / physiology
  • Cell Division / genetics
  • Genes, myc / genetics*
  • Genes, rel*
  • Homeostasis
  • Lipopolysaccharides / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NF-kappa B / deficiency
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Oncogene Proteins v-rel / deficiency
  • Oncogene Proteins v-rel / genetics
  • Oncogene Proteins v-rel / physiology*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Transcription, Genetic*


  • Lipopolysaccharides
  • NF-kappa B
  • Oncogene Proteins v-rel
  • Phosphatidylinositol 3-Kinases