Kinetics of the apoptotic response induced by anti-IgM engagement of the B cell receptor is dependent on the density of cell surface immunoglobulin M expression

The effect of B cell receptor (BCR) density on anti-BCR-induced apoptosis was assessed in Ramos cell lines, expressing low, medium, or high levels of surface IgM (sIgM(LO), SIgM(MED), sIgM(HI)). All cells required a 60-mug/ml threshold of anti-IgM to elicit apoptosis. Anti-IgM treatment of sIgM(LO) cells induced growth inhibition and limited dose-independent apoptosis. Anti-IgM treatment of sIgM(MED) cells induced dose-independent death with a 32-h lag. Ligation of the BCR in the sIgM(HI) cells induced rapid apoptosis beginning by 6 h, which was dose-dependent. Secondary crosslinking reagents did not affect apoptosis, and this effect was independent of anti-IgM concentration, time, or sIgM density. These results suggest that the response to BCR engagement strongly depends on the cell surface receptor density.