NF-κB is dispensable for normal lymphocyte development in bone marrow but required for protection of progenitors from TNFα

Hideya Igarashi, Yoshihiro Baba, Yoshinori Nagai, Eijiro Jimi, Sankar Ghosh, Paul W. Kincade

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

Levels of the nuclear factor-kappa B (NF-κB)/Rel family of proteins are carefully modulated in differentiating lymphocytes, where these transcription factors are thought to be important for survival and fate decisions. In contrast, gene-targeting experiments have not revealed clear roles for these transcription factors in lymphopoiesis within bone marrow. Inhibition of NF-κB by introduction of mutated IκBα, a 'superinhibitor' of NF-κB, into hematopoietic stem cells or early progenitors suppressed B as well as T lymphopoiesis following transplantation into immunodeficient mice. Furthermore, a NF-κB essential modifier-binding domain (NBD) peptide that blocks IKB kinase (IKK) activity selectively impaired the generation of adult B lineage cells. However, this suppression did not occur when a neutralizing antibody to tumor necrosis factor α (TNFα) was added to the cultures, or in circumstances where few non-lymphoid cells were present. We conclude that while NF-κB plays a survival-promoting role in lymphoid progenitors, this may only be significant in circumstances such as transplantation when levels of TNFα are high.

Original languageEnglish
Pages (from-to)653-659
Number of pages7
JournalInternational Immunology
Volume18
Issue number5
DOIs
Publication statusPublished - May 15 2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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