TY - JOUR
T1 - NF-κB is dispensable for normal lymphocyte development in bone marrow but required for protection of progenitors from TNFα
AU - Igarashi, Hideya
AU - Baba, Yoshihiro
AU - Nagai, Yoshinori
AU - Jimi, Eijiro
AU - Ghosh, Sankar
AU - Kincade, Paul W.
N1 - Funding Information:
We acknowledge expert technical assistance provided by Karla P. Garrett, Sophia C. Gregory, Jacob Bass, Diana Hamilton and Viji Dandapani. Finally, we appreciate the secretarial help provided by Shelli Wasson. This work was supported by grants AI20069, AI58162, P20RR15577 and AI33443 (S.G.) from the National Institutes of Health. P.W.K. holds the William H. and Rita Bell Chair in biomedical research.
PY - 2006/5/15
Y1 - 2006/5/15
N2 - 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.
AB - 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.
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U2 - 10.1093/intimm/dxl002
DO - 10.1093/intimm/dxl002
M3 - Article
C2 - 16571606
AN - SCOPUS:33646869954
VL - 18
SP - 653
EP - 659
JO - International Immunology
JF - International Immunology
SN - 0953-8178
IS - 5
ER -