Activation of the transcription factor NF-κB and pre-T cell receptor (pre-TCR) expression is tightly correlated during thymocyte development. Inhibition of NF-κB in isolated thymocytes in vitro results in spontaneous apoptosis of cells expressing the pre-TCR, whereas inhibition of NF-κB in transgenic mice through expression of a mutated, superrepressor form of IκBα leads to a loss of β-selected thymocytes. In contrast, the forced activation of NF-κB through expression of a dominant-active I κB 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-κB, which provides a selective survival signal for developing thymocytes with productive chain rearrangements.
All Science Journal Classification (ASJC) codes
- Immunology and Allergy
- Infectious Diseases