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International Immunology Advance Access published online on March 29, 2006
International Immunology, doi:10.1093/intimm/dxl002
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© The Japanese Society for Immunology. 2006. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org
Received July 1, 2005
Accepted January 27, 2006

Article

NF-{kappa}B is dispensable for normal lymphocyte development in bone marrow but required for protection of progenitors from TNF{alpha}

Hideya Igarashi 1 *, Yoshihiro Baba 1 *, Yoshinori Nagai 1, Eijiro Jimi 2, Sankar Ghosh 2, and Paul W. Kincade 1 *

1 Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA
2 Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA

* To whom correspondence should be addressed.
Paul W. Kincade, E-mail: kincade{at}omrf.ouhsc.edu


  Abstract

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.

Keywords: adult bone marrow; fetal liver; lymphopoiesis; NF-{kappa}B; TNF{alpha}.

*These authors contributed equally to this work.


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