B lymphocytes inhibit human osteoclastogenesis by secretion of TGFbeta.
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 beta (TGFbeta), a factor that induces apoptosis in these cells. The antiosteoclastogenic effects of B cells are abolished by addition of anti-TGFbeta antibody to osteoclast cultures and mimicked by treatment of B cell-deprived PBSC cultures with recombinant TGFbeta, thus confirming TGFbeta as the B cell produced antiosteoclastogenic activity. Thus, the ability of B cells to downregulate osteoclastogenesis by secretion of the apoptotic cytokine TGFbeta provides new insights into the ability of immune cells to regulate OC formation under basal and inflammatory conditions.
Weitzmann
M N
MN
Division of Bone and Mineral Diseases, Washington University School of Medicine and Barnes-Jewish Hospital, St. Louis, Missouri 63110, USA.
Cenci
S
S
Haug
J
J
Brown
C
C
DiPersio
J
J
Pacifici
R
R
D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology*; D001862:Bone Resorption / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation; D002460:Cell Line; D016922:Cellular Senescence; D017077:Culture Media, Conditioned; D006801:Humans; D066298:In Vitro Techniques; D010010:Osteoclasts / Q000166:cytology* / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology
D017077:Culture Media, Conditioned; D016212:Transforming Growth Factor beta