Stimulation of thymocytes before and after positive selection results in the induction of different NF-kappa B/Rel protein complexes.
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.
Moore
N C
NC
Centre for Clinical Research in Immunology & Signalling, Medical School, University of Birmingham, United Kingdom.
Girdlestone
J
J
Anderson
G
G
Owen
J J
JJ
Jenkinson
E J
EJ
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D005786:Gene Expression Regulation; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000096:biosynthesis*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D016176:T-Lymphocyte Subsets
D016328:NF-kappa B; D011948:Receptors, Antigen, T-Cell