Journal
INTERNATIONAL IMMUNOLOGY
Volume 18, Issue 5, Pages 653-659Publisher
OXFORD UNIV PRESS
DOI: 10.1093/intimm/dxl002
Keywords
adult bone marrow; fetal liver; lymphopoiesis; NF-kappa B; TNF alpha
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Funding
- NCRR NIH HHS [P20RR15577] Funding Source: Medline
- NIAID NIH HHS [AI58162, AI20069, R37 AI033443, AI33443] Funding Source: Medline
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Levels of the nuclear factor-kappa B (NF-kappa B)/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-kappa B by introduction of mutated I kappa B alpha, a 'superinhibitor' of NF-kappa B, into hematopoietic stem cells or early progenitors suppressed B as well as T lymphopoiesis following transplantation into immunodeficient mice. Furthermore, a NF-kappa B 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 alpha (TNF alpha) was added to the cultures, or in circumstances where few non-lymphoid cells were present. We conclude that while NF-kappa B plays a survival-promoting role in lymphoid progenitors, this may only be significant in circumstances such as transplantation when levels of TNF alpha are high.
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