Re. Voll et al., NF-kappa B activation by the pre-T cell receptor serves as a selective survival signal in T lymphocyte development, IMMUNITY, 13(5), 2000, pp. 677-689
Activation of the transcription factor NF-kappaB and pre-T cell receptor (p
re-TCR) expression is tightly correlated during thymocyte development. inhi
bition of NF-kappaB in isolated thymocytes in vitro results in spontaneous
apoptosis of cells expressing the pre-TCR, whereas inhibition of NF-kappaB
in transgenic mice through expression of a mutated, superrepressor form of
I kappaB alpha leads to a loss of beta -selected thymocytes. In contrast, t
he forced activation of NF-kappaB through expression of a dominant-active I
kappaB kinase allows differentiation to proceed to the CD4(+)CD8(+) stage
in a Rag1(-/-) mouse that cannot assemble the pre-TCR. Therefore, signals e
manating from the pre-TCR are mediated at least in part by NF-kappaB, which
provides a selective survival signal for developing thymocytes with produc
tive beta chain rearrangements.