Diacylglycerol (DAG) is a second messenger produced downstream of multiple receptors by activation of phospholipase C-γ (PLC-γ). In Science Signaling, DeFranco and colleagues show that DAG sets a threshold for the activation of follicular B cells. Expression of diacylglycerol kinase-ζ (DGK-ζ), which terminates DAG-dependent signaling by converting DAG into phosphatidic acid, increases as transitional B cells mature. DGK-ζ regulates the abundance of DAG needed to activate downstream pathways after stimulation of the BCR. Notably, signaling dependent on the kinase Erk is more sensitive to DAG than is signaling via the transcription factor NF-κB. Mice bearing B cells that lack DGK-ζ have more replicating B cells and plasma cells and higher titers of circulating antibody, as the threshold for B cell activation is lower in these mice than in wild-type mice. Thus, DGK-ζ tunes the response of mature B cells by setting a threshold for DAG to activate Erk-dependent pathways.

Sci. Signal. (15 October 2013) doi:10.1126/scisignal.2004189