The survival of long-lived bone marrow plasma cells (PCs) is essential for maintaining long-term humoral immunity. This study demonstrates that BLyS (B lymphocyte stimulator) and APRIL support PC survival in vitro and in vivo. BLyS enhances PC survival by up-regulating Mcl-1, an anti-apoptotic gene, and by binding to BCMA, a receptor expressed on PCs. Blockade of BLyS with TACI-Ig inhibits PC survival, indicating the importance of BLyS in PC survival. BCMA is critical for PC survival, as shown by the reduced number of long-lived BM PCs in BCMA-deficient mice. These findings suggest that BCMA is essential for the survival of long-lived BM PCs, and that BLyS and APRIL, through their interaction with BCMA, are critical for PC survival. The study also shows that BCMA is highly expressed in PCs compared to resting B cells, and that BCMA is necessary for the survival of long-lived BM PCs. The results highlight the importance of BCMA in PC survival and suggest that targeting BCMA could be a potential therapeutic strategy for antibody-mediated autoimmunity.The survival of long-lived bone marrow plasma cells (PCs) is essential for maintaining long-term humoral immunity. This study demonstrates that BLyS (B lymphocyte stimulator) and APRIL support PC survival in vitro and in vivo. BLyS enhances PC survival by up-regulating Mcl-1, an anti-apoptotic gene, and by binding to BCMA, a receptor expressed on PCs. Blockade of BLyS with TACI-Ig inhibits PC survival, indicating the importance of BLyS in PC survival. BCMA is critical for PC survival, as shown by the reduced number of long-lived BM PCs in BCMA-deficient mice. These findings suggest that BCMA is essential for the survival of long-lived BM PCs, and that BLyS and APRIL, through their interaction with BCMA, are critical for PC survival. The study also shows that BCMA is highly expressed in PCs compared to resting B cells, and that BCMA is necessary for the survival of long-lived BM PCs. The results highlight the importance of BCMA in PC survival and suggest that targeting BCMA could be a potential therapeutic strategy for antibody-mediated autoimmunity.