Voll R E, Jimi E, Phillips R J, Barber D F, Rincon M, Hayday A C, Flavell R A, Ghosh S
Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Immunity. 2000 Nov;13(5):677-89. doi: 10.1016/s1074-7613(00)00067-4.
Activation of the transcription factor NF-kappa B and pre-T cell receptor (pre-TCR) expression is tightly correlated during thymocyte development. Inhibition of NF-kappa B in isolated thymocytes in vitro results in spontaneous apoptosis of cells expressing the pre-TCR, whereas inhibition of NF-kappa B in transgenic mice through expression of a mutated, superrepressor form of I kappa B alpha leads to a loss of beta-selected thymocytes. In contrast, the forced activation of NF-kappa B through expression of a dominant-active I kappa B kinase allows differentiation to proceed to the CD4(+)CD8(+) stage in a Rag1(-/-) mouse that cannot assemble the pre-TCR. Therefore, signals emanating from the pre-TCR are mediated at least in part by NF-kappa B, which provides a selective survival signal for developing thymocytes with productive beta chain rearrangements.
在胸腺细胞发育过程中，转录因子NF-κB的激活与前T细胞受体（pre-TCR）的表达密切相关。体外分离的胸腺细胞中NF-κB的抑制导致表达pre-TCR的细胞自发凋亡，而通过表达突变的、超抑制形式的IκBα在转基因小鼠中抑制NF-κB会导致β选择的胸腺细胞丢失。相反，通过表达显性活性IκB激酶强制激活NF-κB可使无法组装pre-TCR的Rag1(-/-)小鼠中的分化进程至CD4(+)CD8(+)阶段。因此，来自pre-TCR的信号至少部分由NF-κB介导，NF-κB为具有有效β链重排的发育中的胸腺细胞提供选择性存活信号。
