PLC-γ2 is a key regulator of degranulation. (A) Freshly DX5-enriched NK cells (70%-80% purity) were incubated for 5 hours, in the presence of anti-CD107a, with nothing, YAC-1 targets, or PMA and ionomycin, as indicated. Only cells that have degranulated expose CD107a on the cell surface. Target cells induced degranulation in WT but not Plcg2^-/- NK cells. (B) WT (▪) and Plcg2^-/- (□) NK cells were stimulated with anti-NK1.1 mAb or isotype-matched control and after 4 hours the specific esterase activity was measured by BLT-colorimetric assay. Maximal release in NK cell lysates obtained after freeze-thaw cycles was similar in WT and Plcg2^-/- NK cells (not shown). Data are means ± SD of 2 independent experiments, including a total of 4 individual mice per group.