The aim of this in vitro study was to evaluate if osteoclasts (OCs) and dendritic cells (DCs), both of monocyte origin, can support the survival of normal human plasma cells (PCs). PCs differentiate from plasmablasts (PBs) arising from activated B cells, essentially memory B cells. To study the survival of both PBs (CD20(low)CD38(high)CD138(neg)) and PCs (CD20(neg)CD38(bright)CD138(bright)), we generated pre-PBs (CD20(low)CD38(pos)CD138(neg)) from CD40-activated B cells (CD20(high)CD38(neg)CD138(neg)) and cultured them on DCs or OCs in the presence of added IL-6. By quantitative and qualitative study, we showed that DCs support the survival of PBs and early PCs, but not that of PCs. In contrast, OCs support the survival of PBs, early PCs and PCs. PCs surviving on OCs 12 days after pre-PB input display phenotypic features of bone marrow PCs, CD138(bright)CD38(bright)HLA-DR(low)CD45(dim). The ability for OCs to support the survival of PCs was fully dependent on cell-cell contact and not inhibited by BCMA-Fc suggesting that secreted BAFF and APRIL were not involved.