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

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Abstract
Transgenic mice expressing a T‐cell‐specific dominant interfering allele (MEnT) 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 β‐selection, the process by which productive rearrangement of the T‐cell receptor (TCR) β‐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 regulating β‐selection. It is also expressed in the absence of cytokine signalling. However, we show that c‐Myb protein is required for the function in β‐selection of its known upstream activator, the serine/threonine kinase Pim1: MEnT expression inhibits the cell cycle in Pim1 transgenic DN thymocytes and prevents Pim1‐mediated rescue of a RAG1−/− developmental block. Super activation of c‐Myb by Pim1 may therefore be required for β‐selection.