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The Journal of Immunology, Vol 155, Issue 10 4653-4660, Copyright © 1995 by American Association of Immunologists
ARTICLES |
NC Moore, J Girdlestone, G Anderson, JJ Owen and EJ Jenkinson
Centre for Clinical Research in Immunology & Signalling, Medical School, University of Birmingham, United Kingdom.
Positive selection triggers the differentiation of immature CD4+8+TCRlow thymocytes into TCRhigh single-positive CD4+ or CD8+ cells and is associated with major changes in gene expression. However, little is known about the DNA binding factors controlling these fundamental changes. Here we have examined NF-kappa B/Rel subunit expression and DNA-binding activity in developing thymocytes before and after the induction of positive selection. We show that positive selection is accompanied by the strong up-regulation of c-rel mRNA expression and the constitutive activation of p50/p65 and p50/c-Rel NF- kappa B/Rel complexes, confirming the activation-like status of cells undergoing positive selection. Moreover, CD69+ cells that have initiated positive selection (but not their preselection CD4+8+TCR- precursors) respond to stimulation by the preferential activation of c- Rel-containing DNA-binding complexes. Because the different NF-kappa B/Rel dimers have distinct transcriptional activities and binding site preferences, this preferential activation of c-Rel-containing DNA- binding complexes may well have implications for the changes in gene expression and functional response associated with positive selection.
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