The survival of long-lived plasma cells, which produce most serum immunoglobulin, is central to humoral immunity. We found here that the inhibitory Fc receptor FcγRIIb was expressed on plasma cells and controlled their persistence in the bone marrow. Crosslinking FcγRIIb induced apoptosis of plasma cells, which we propose contributes to the control of their homeostasis and suggests a method for therapeutic deletion. Plasma cells from mice prone to systemic lupus erythematosus did not express FcγRIIb and were protected from apoptosis. Human plasmablasts expressed FcγRIIb and were killed by crosslinking, as were FcγRIIb-expressing myeloma cells. Our results suggest that FcγRIIb controls bone marrow plasma cell persistence and that defects in it may contribute to autoantibody production.