International Immunology Advance Access originally published online on March 29, 2006
International Immunology 2006 18(5):653-659; doi:10.1093/intimm/dxl002
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NF-
B is dispensable for normal lymphocyte development in bone marrow but required for protection of progenitors from TNF
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
Correspondence to: P. W. Kincade; E-mail: kincade{at}omrf.ouhsc.edu
Levels of the nuclear factor-kappa B (NF-
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-B by introduction of mutated IB
, a ‘superinhibitor’ of NF-B, into hematopoietic stem cells or early progenitors suppressed B as well as T lymphopoiesis following transplantation into immunodeficient mice. Furthermore, a NF-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 (TNF) was added to the cultures, or in circumstances where few non-lymphoid cells were present. We conclude that while NF-B plays a survival-promoting role in lymphoid progenitors, this may only be significant in circumstances such as transplantation when levels of TNF are high.
Keywords: adult bone marrow, fetal liver, lymphopoiesis, NF-B, TNF
* These authors contributed equally to this work.
Transmitting editor: T. F. Tedder
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