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,
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Departments of
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Immunology,
Microbiology, and
Orthodontics, and
Regional Primate Research Center, University of Washington, Seattle, WA 98195;
¶ Division of Basic Sciences and Program in Developmental Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109; and
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Max Delbrueck Center for Molecular Medicine, Berlin, Germany
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.
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