c-Myb regulates the proliferation of immature thymocytes following beta-selection

Transgenic mice expressing a T-cell-specific dominant interfering allele (M EnT) of the c-Myb transcription factor have a pronounced block in CD4(-)CD8 (-) (DN) development. In this study we show that differentiation of DN MEnT thymocytes is blocked due to the failure of cells to enter the cell cycle following beta -selection, the process by which productive rearrangement of the T-cell receptor (TCR) beta -chain permits maturation of cells into CD4 (+)CD8(+) (DP) thymocytes. c-myb mRNA continues to be expressed in DN cells in mice lacking a functional pre-TCR signalling pathway, implying that its transcriptional regulation is independent of the signalling events regulat ing beta -selection. It is also expressed in the absence of cytokine signal ling. However, we show that c-Myb protein is required for the function in b eta -selection of its known upstream activator, the serine/threonine kinase Pim1: MEnT expression inhibits the cell cycle in Pim1 transgenic DN thymoc ytes and prevents Pim1-mediated rescue of a RAG1(-/-) developmental block. Super-activation of c-Myb by Pim1 may therefore be required for beta -selec tion.