Effects of NMDAR antagonists on B-cell proliferation and apoptosis. A-D) NMDAR antagonists impair BCR-, TLR4- and PMA/IO-induced B-cell proliferation. Splenic B cells were stimulated with A) α-IgM (10 µg/ml) B) LPS (10 µg/ml), C) PMA and ionomycin (IO) or D) α-IgM or LPS in combination with CD40 Abs (5 µg/ml) in the presence or absence of the indicated concentrations of memantine, ifenprodil or D-APV. Proliferation was determined by 3[H]-Thymidine incorporation (cpm) at 24 h. Data in the graphs represent the mean + SD relative proliferation of at least two experiments. E) NMDAR antagonists enhance B-cell apoptosis. B cells were stimulated with α-IgM or LPS plus/minus CD40 Abs in the presence or absence of ifenprodil or memantine (30 μM each) for 24 h. Apoptosis was measured with Annexin V and propidium iodide (PI) staining and flow cytometry. The percentage of AnnexinV+ PI− early and AnnexinV+PI+ late apoptotic cells is indicated in the dot plots (left). Data in the right graphs show the percentage of apoptotic cells as mean + SD calculated from two experiments.