Control of early thymocyte development by the pre-T cell receptor complex: A receptor without a ligand?

β-selection refers to a developmental checkpoint linking thymocyte survival to the outcome of antigen receptor gene rearrangement. Immature thymocytes that productively rearrange the gene segments of the TCRβ locus undergo proliferative expansion and mature to the CD⁴⁺ CD⁸⁺ stage; those failing to do so die by apoptosis. How are these precursor cells alerted that TCRβP rearrangement has been productive? While it is clear that this process involves signals transduced by a surrogate form of the TCR termed the pre-TCR, it remains unclear how pre-TCR signals are triggered. In this review, we will discuss the implications of recent experimental attempts to address this issue, as well as how pre-TCR activation is linked to the changes in gene expression that underlie thymocyte development.