c-Myb regulates lineage choice in developing thymocytes via its target gene Gata3

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Abstract
During T‐cell development, thymocytes with intermediate avidity for antigen–MHC complexes are positively selected and then differentiate into functional cytotoxic and helper T cells. This process is controlled by signalling from the T‐cell receptor (TCR). Here, we show that the c‐Myb transcription factor is a critical downstream regulator of positive selection, promoting the development of helper T cells and blocking the development of cytotoxic T cells. A gain‐of‐function c‐Myb transgene stops development of cytotoxic T cells, instead causing accumulation of a precursor population. Conversely, loss of c‐Myb in selecting cells results in significantly fewer helper T cells. In c‐Myb ‐null thymocytes, Gata3 , a critical inducer of T‐helper cell fate, is not upregulated in response to T‐cell receptor signaling, following selection. We show that Gata3 is a direct target of c‐Myb, and propose that c‐Myb is an important regulator of Gata3 , required for transduction of the T‐cell receptor signal for subsequent helper cell lineage differentiation.