B lymphocytes inhibit human osteoclastogenesis by secretion of TGF beta

The role of B lymphocytes in osteoclast (OC) formation is controversial, be cause both stimulatory and Inhibitory effects of B-lineage cells on osteocl astogenesis and life span have been reported. In this study, we have Invest igated the effects of mature B cells on human osteoclastogenesis using cult ures of peripheral blood stem cells (PBSC), a system that generates functio nal OCs in the absence of stromal cells. We report that B cells inhibit the formation or OCs and shorten the life span of mature OCs by secreting tran sforming growth factor beta (TGF beta), a factor that induces apoptosis in these cells. The antiosteoclastogenic effects of B cells are abolished by a ddition of anti-TGF beta antibody to osteoclast cultures and mimicked by tr eatment of B cell-deprived PBSC cultures with recombinant TGF beta, thus co nfirming TGF beta as the B cell produced antiosteoclastogenic activity. Thu s, the ability of B cells to downregulate osteoclastogenesis by secretion o f the apoptotic cytokine TCF beta provides new insights into the ability of immune cells to regulate OC formation under basal and inflammatory conditi ons. (C) 2000 Wiley-Liss. Inc.