Thymocytes must pass a series of checkpoints on the road to becoming mature T cells. On page 603, Mandal et al. show that cells use Bcl2A1, a member of the Bcl2 family of survival proteins, to pass one critical checkpoint. The cell cannot make substitutes for this protein in a pinch, revealing that Bcl2A1 may be uniquely specialized for promoting survival without suppressing proliferation.
To become mature T cells, thymocytes must express a functional T cell receptor (TCR). A requisite early step in fulfilling this goal is the expression of the pre-TCR—the β chain of the mature TCR coupled with a pre–α chain—which sends essential survival and proliferation signals to the developing cell. Activation of NF-κB was shown recently to be required at this checkpoint, known as β-selection, but beyond that the components of this survival signal have remained elusive.
In an attempt to...
