NF-κB activation by the pre-T cell receptor serves as a selective survival signal in T lymphocyte development

Activation of the transcription factor NF-kappaB and pre-T cell receptor (pre-TCR) expression is tightly correlated during thymocyte development. inhibition 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, the 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 emanating from the pre-TCR are mediated at least in part by NF-kappaB, which provides a selective survival signal for developing thymocytes with productive beta chain rearrangements.