Regulation of Vbeta germline transcription in RAG-deficient mice by the CD3epsilon-mediated signals: implication of Vbeta transcriptional regulation in TCR beta allelic exclusion.
During the thymic development of alphabeta lineage T cells, maturation of the CD4- CD8- double-negative (DN) cells into the CD4+ CD8+ double-positive cells is accompanied by the induction of TCR beta allelic exclusion. Recent studies have shown that these events are regulated by the signals through the pre-TCR complex which consists of the TCR beta, pre-TCR alpha and CD3 components. The Vbeta germline transcripts are detected prior to the TCR beta chain gene rearrangements in the DN thymocytes. To examine the effects of the pre-TCR-mediated signals on Vbeta germline transcription, we analyzed thymocytes from RAG-2-deficient mice treated with anti-CD3epsilon antibody. The germline transcripts of all Vbeta we examined, except for Vbeta14, were down-regulated by the anti-CD3epsilon antibody treatment. These data indicate that the regulation of Vbeta germline transcription by the signals through the pre-TCR complex may reflect the modulation of Vbeta accessibility to the VDJ recombinase, which contributes to TCR beta allelic exclusion.
Senoo
M
M
Department of Molecular Oncology, Nippon Roche Research Center, Kamakura-city, Kanagawa, Japan.
Shinkai
Y
Y
D000483:Alleles; D000818:Animals; D001483:Base Sequence; D017252:CD3 Complex / Q000235:genetics*; D019175:DNA Methylation; D004254:DNA Nucleotidyltransferases / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014158:Transcription, Genetic; D045567:VDJ Recombinases
D017252:CD3 Complex; D017931:DNA Primers; D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; D016693:Receptors, Antigen, T-Cell, alpha-beta; C064655:V(D)J recombination activating protein 2; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases