NF-κB activation by the pre-T cell receptor serves as a selective survival signal in T lymphocyte development

Reinhard E. Voll, Eijiro Jimi, Roderick J. Phillips, Domingo F. Barber, Mercedes Rincon, Adrian C. Hayday, Richard A. Flavell, Sankar Ghosh

Research output: Contribution to journalArticlepeer-review

235 Citations (Scopus)

Abstract

Activation of the transcription factor NF-κB and pre-T cell receptor (pre-TCR) expression is tightly correlated during thymocyte development. Inhibition of NF-κB in isolated thymocytes in vitro results in spontaneous apoptosis of cells expressing the pre-TCR, whereas inhibition of NF-κB in transgenic mice through expression of a mutated, superrepressor form of IκBα leads to a loss of β-selected thymocytes. In contrast, the forced activation of NF-κB through expression of a dominant-active I κB kinase allows differentiation to proceed to the CD4+CD8+ stage in a Rag1(-/-) mouse that cannot assemble the pre-TCR. Therefore, signals emanating from the pre-TCR are mediated at least in part by NF-κB, which provides a selective survival signal for developing thymocytes with productive chain rearrangements.

Original languageEnglish
Pages (from-to)677-689
Number of pages13
JournalImmunity
Volume13
Issue number5
DOIs
Publication statusPublished - 2000

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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