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.
Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Hideya
H
Igarashi
Yoshihiro
Y
Baba
Yoshinori
Y
Nagai
Eijiro
E
Jimi
Sankar
S
Ghosh
Paul W
PW
Kincade
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