期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：26
页码：15800-15805
DOI：10.1073/pnas.2535880100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：In most cells, the NF-{kappa}B transcription factor is sequestered in the cytoplasm by interaction with inhibitory proteins, the I{kappa}Bs. Here, we show that combined I{kappa}B/I{kappa}B{varepsilon} deficiency in mice leads to neonatal death, elevated {kappa}B binding activity, overexpression of NF-{kappa}B target genes, and disruption of lymphocyte production. In I{kappa}B/I{kappa}B{varepsilon}-deficient fetuses, B220+IgM+ B cells and single-positive T cells die by apoptosis. In adults, I{kappa}B-/-I{kappa}B{varepsilon}-/- reconstituted chimeras exhibit a nearly complete absence of T and B cells that is not rescued by cotransfer with wild-type bone marrow. These findings demonstrate that I{kappa}Bs tightly control NF-{kappa}B activity in vivo and that increased NF-{kappa}B activity intrinsically impairs lymphocyte survival. Because reduction or rise of NF-{kappa}B activity leads to similar dysfunction, they also reveal that only a narrow window of NF-{kappa}B activity is tolerated by lymphocytes.
