TCRγ Silencing during αβ T Cell Development Depends upon Pre-TCR-Induced Proliferation

Abstract

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