STIMULATION OF THYMOCYTES BEFORE AND AFTER POSITIVE SELECTION RESULTSIN THE INDUCTION OF DIFFERENT NF-KAPPA-B REL PROTEIN COMPLEXES/

Positive selection triggers the differentiation of immature CD4(+)8(+) TCR(low) thymocytes into TCR(high) single-positive CD4(+) or CD8(+) ce lls and is associated with major changes in gene expression. However, little is known about the DNA binding factors controlling these fundam ental changes. Here we have examined NF-kappa B/Rel subunit expression and DNA-binding activity in developing thymocytes before and after th e induction of positive selection. We show that positive selection is accompanied by the strong up-regulation of c-rel mRNA expression and t he constitutive activation of p50/p65 and p50/c-Rel NF-kappa B/Rel com plexes, confirming the activation-like status of cells undergoing posi tive selection. Moreover, CD69(+) cells that have initiated positive s election (but not their preselection CD4(+)8(+)TCR(-) precursors) resp ond to stimulation by the preferential activation of c-Rel-containing DNA-binding complexes. Because the different NF-kappa B/Rel dimers hav e distinct transcriptional activities and binding site preferences, th is preferential activation of c-Rel-containing DNA-binding complexes m ay well have Implications for the changes in gene expression and funct ional response associated with positive selection.