Aberrant expression of the TCL1 oncoprotein promotes malignant transformation of germinal center (GC) B cells. Repression ofTCL1in GC B cells facilitates FAS-mediated apoptosis and prevents lymphoma formation. However, the mechanism for this repression is unknown. Here we show that the CREB coactivator TORC2 directly regulatesTCL1expression independent of CREB Ser-133 phosphorylation and CBP/p300 recruitment. GC signaling through CD40 or the BCR, which activates pCREB-dependent genes, caused TORC2 phosphorylation, cytosolic emigration, andTCL1repression. Signaling via cAMP-inducible pathways inhibitedTCL1repression and reduced apoptosis, consistent with a prosurvival role for TCL1 before GC selection and supporting an initiating role for aberrantTCL1expression during GC lymphomagenesis. Our data indicate that a novel CREB/TORC2 regulatory mode controls the normal program of GC gene activation and repression that promotes B cell development and circumvents oncogenic progression. Our results also reconcile a paradox in which signals that activate pCREB/CBP/p300 genes concurrently repressTCL1to initiate its silencing.