Live free or die: an immature T cell decision encoded in distinct Bcl-2 sensitive and insensitive Ca2+ signals

In the developing thymus, strong T cell receptor (TCR) activation by self-antigens induces negative selection and weak TCR activation induces positive selection. Both processes are mediated by Ca(2+) signals, raising the question of how a single second messenger like Ca(2+) can mediate such diverse cell fates. Recent findings indicate that graded TCR activation signals are encoded in distinct patterns of Ca(2+) elevation. The anti-apoptotic protein Bcl-2 discriminates between these Ca(2+) signaling patterns, selectively inhibiting pro-apoptotic Ca(2+) signals induced by strong TCR activation without suppressing pro-survival Ca(2+) signals induced by weak TCR activation.