FcγRIIb controls bone marrow plasma cell persistence and apoptosis

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 Fc gamma RIIb was expressed on plasma cells and controlled their persistence in the bone marrow. Crosslinking Fc gamma RIIb 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 Fc gamma RIIb and were protected from apoptosis. Human plasmablasts expressed Fc gamma RIIb and were killed by crosslinking, as were Fc gamma RIIb-expressing myeloma cells. Our results suggest that Fc gamma RIIb controls bone marrow plasma cell persistence and that defects in it may contribute to autoantibody production.