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 cel ls (DCs). We investigated the role of OPG in the immune system by generatin g opg(-/-) mice. Like its role as a regulator of bone metabolism, OPG also influences processes in the immune system, notably in B cell development. E x vivo, opg(-/-) pro-B cells have enhanced proliferation to IL-7, and in op g(-/-) spleen, there is an accumulation of type 1 transitional B cells. Fur thermore, opg(-/-) bone marrow-derived DCs are more effective in stimulatin g allogeneic T cells than control DCs. When challenged with a T-dependent A g, opg(-/-) mice had a compromised ability to sustain an IgG3 Ag-specific r esponse. Thus, in the immune system, OPG regulates B cell maturation and de velopment of efficient Ab responses.