TGF beta 1 inhibits NF-kappa B/Rel activity inducing apoptosis of B cells: transcriptional activation of I kappa B alpha

Immunity. 1996 Jul;5(1):31-40. doi: 10.1016/s1074-7613(00)80307-6.


TGF beta 1 treatment of B cell lymphomas decreases c-myc gene expression and induces apoptosis. Since we have demonstrated NF-kappa/Rel factors play a key role in transcriptional control of c-myc, we explored the effects of TGF beta1 on WEHI 231 immature B cells. A reduction in NF-kappa B/Rel activity followed TGF beta 1 treatment. In WEHI 231 and CH33 cells, we observed an increase in I kappa B alpha, a specific NF-kappa B/Rel inhibitor, due to transcriptional induction. Engagement of surface CD40 or ectopic c-Rel led to maintenance of NF-kappa B/Rel and c-Myc expression and protection of WEHI 231 cells from TGF beta 1-mediated apoptosis. Ectopic c-Myc expression overrode apoptosis induced by TGF beta 1. Thus, downmodulation of NF-kappa B/Rel reduces c-Myc expression, which leads to apoptosis in these immature B cell models of clonal deletion. The inhibition of NF-kappa B/Rel activity represents a novel TGF beta signaling mechanism.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / metabolism
  • CD40 Ligand
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Genes, myc / immunology
  • Ligands
  • Membrane Glycoproteins / pharmacology
  • Mice
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / biosynthesis
  • Proto-Oncogene Proteins / antagonists & inhibitors*
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins c-rel
  • RNA, Messenger / biosynthesis
  • Transcription Factor RelB
  • Transcription Factors*
  • Transcription, Genetic / immunology*
  • Transforming Growth Factor beta / pharmacology*
  • Tumor Cells, Cultured


  • Ligands
  • Membrane Glycoproteins
  • NF-kappa B
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-rel
  • RNA, Messenger
  • Relb protein, mouse
  • Transcription Factors
  • Transforming Growth Factor beta
  • CD40 Ligand
  • Transcription Factor RelB