NF-kappaB is dispensable for normal lymphocyte development in bone marrow but required for protection of progenitors from TNFalpha.
Levels of the nuclear factor-kappa B (NF-kappaB)/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-kappaB by introduction of mutated I kappa B alpha, a 'superinhibitor' of NF-kappaB, into hematopoietic stem cells or early progenitors suppressed B as well as T lymphopoiesis following transplantation into immunodeficient mice. Furthermore, a NF-kappaB 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 (TNFalpha) was added to the cultures, or in circumstances where few non-lymphoid cells were present. We conclude that while NF-kappaB plays a survival-promoting role in lymphoid progenitors, this may only be significant in circumstances such as transplantation when levels of TNFalpha are high.
Igarashi
Hideya
H
Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Baba
Yoshihiro
Y
Nagai
Yoshinori
Y
Jimi
Eijiro
E
Ghosh
Sankar
S
Kincade
Paul W
PW
D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology* / Q000276:immunology; D002454:Cell Differentiation / Q000502:physiology; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology; D038041:Lymphopoiesis / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D012190:Retroviridae / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha