Proteostenosis and plasma cell pathophysiology

Plasma cells differentiate from B lymphocytes to sustain antibody production. As professional secretors, they allow dissecting proteostasis in the exocytic compartment, the stresses that protein production entails and their possible roles in signaling. Most plasma cells are short-lived to limit antibody responses. After a few days of intense immunoglobulin production, they undergo apoptosis, offering a unique model of cellular senescence. Recent observations reveal that proteotoxic stresses physiologically contribute to regulate their biogenesis, function and lifespan, explaining partly the sensitivity of multiple myeloma cells to proteasome inhibitors. This essay summarizes these plasma cell lessons, and their general implications for the regulation of proteostasis, cell senescence and cancer therapeutics.