TCRγ silencing during αβ T cell development depends upon pre-TCR-induced proliferation

During thymus development, immature T cells become committed to two distinct lineages based upon expression of alpha beta or gamma delta TCR. In the all lineage, developing thymocytes progressively extinguish transcription of the TCR gamma genes by a poorly understood process known as gamma silencing. We show that alpha beta lineage thymocytes in mice lacking a functional pre-TCR undergo limited proliferation and fail to silence TCR gamma genes during development. Stimulation of pre-TCR-deficient immature thymocytes with anti-CD3 Abs does not directly down-regulate TCR gamma transcription but restores TCR gamma silencing following proliferation. Collectively our data reveal an important role for pre-TCR induced proliferation in activating the TCR gamma silencer in alpha beta lineage thymocytes, a process that may reinforce alpha beta or gamma delta lineage commitment.