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-antigensinduces negative selection and weak TCR activation induces positive selection. Bothprocesses are mediated by Ca2+ signals, raising the question of how a single secondmessenger like Ca2+ can mediate such diverse cell fates. Recent findings indicate thatgraded TCR activation signals are encoded in distinct patterns of Ca2+ elevation. Theanti-apoptotic protein Bcl-2 discriminates between these Ca2+ signaling patterns,selectively inhibiting pro-apoptotic Ca2+ signals induced by strong TCR activationwithout suppressing pro-survival Ca2+ signals induced by weak TCR activation.