The role of B lymphocytes in osteoclast (OC) formation is controversial, because both stimulatory and inhibitory effects of B‐lineage cells on osteoclastogenesis and life span have been reported. In this study, we have investigated the effects of mature B cells on human osteoclastogenesis using cultures of peripheral blood stem cells (PBSC), a system that generates functional OCs in the absence of stromal cells. We report that B cells inhibit the formation of OCs and shorten the life span of mature OCs by secreting transforming growth factor β (TGFβ), a factor that induces apoptosis in these cells. The antiosteoclastogenic effects of B cells are abolished by addition of anti‐TGFβ antibody to osteoclast cultures and mimicked by treatment of B cell‐deprived PBSC cultures with recombinant TGFβ, thus confirming TGFβ as the B cell produced antiosteoclastogenic activity. Thus, the ability of B cells to downregulate osteoclastogenesis by secretion of the apoptotic cytokine TGFβ provides new insights into the ability of immune cells to regulate OC formation under basal and inflammatory conditions. J. Cell. Biochem. 78:318–324, 2000. © 2000 Wiley‐Liss, Inc.