Osteoprotegerin, a crucial regulator of bone metabolism, also regulates B cell development and function.
Osteoprotegerin (OPG) is a CD40-regulated gene in B cells and dendritic cells (DCs). We investigated the role of OPG in the immune system by generating opg(-/-) mice. Like its role as a regulator of bone metabolism, OPG also influences processes in the immune system, notably in B cell development. Ex vivo, opg(-/-) pro-B cells have enhanced proliferation to IL-7, and in opg(-/-) spleen, there is an accumulation of type 1 transitional B cells. Furthermore, opg(-/-) bone marrow-derived DCs are more effective in stimulating allogeneic T cells than control DCs. When challenged with a T-dependent Ag, opg(-/-) mice had a compromised ability to sustain an IgG3 Ag-specific response. Thus, in the immune system, OPG regulates B cell maturation and development of efficient Ab responses.
Yun
T J
TJ
Department of Immunology, and Regional Primate Research Center, University of Washington, Seattle, WA 98195, USA.
Tallquist
M D
MD
Aicher
A
A
Rafferty
K L
KL
Marshall
A J
AJ
Moon
J J
JJ
Ewings
M E
ME
Mohaupt
M
M
Herring
S W
SW
Clark
E A
EA
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D018390:Gene Targeting; D006023:Glycoproteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006410:Hematopoiesis / Q000235:genetics / Q000276:immunology; D017578:Immunoglobulin Class Switching / Q000235:genetics; D007072:Immunoglobulin D / Q000096:biosynthesis; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D018655:Lymphocyte Count; D008218:Lymphocytosis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D010024:Osteoporosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor; D013601:T-Lymphocytes / Q000276:immunology
D006023:Glycoproteins; D007072:Immunoglobulin D; D007132:Immunoglobulin Isotypes; D007075:Immunoglobulin M; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506031:Tnfrsf11b protein, mouse