The authors show that the ligation of CD32a induces DC maturation, exemplified by upregulation of maturation markers, release of specific cytokines and heightened T cell stimulatory capacity. In contrast, ligation of CD32b inhibits DC activation. These data uncover the differential contributions of CD32 isoforms and the potential role they may play in the induction of tolerance versus autoimmunity.
Further, the researchers show that intravenous immune globulin selectively shifts Fc-gamma receptor expression to a CD32b-dominated profile, which provides a mechanism to explain globulin's anti-inflammatory properties in humans. The findings also help account for results reported by some investigators when using mouse IgG with human dendritic cells. These findings have implications for optimizing the efficacy of therapeutic antibodies and suggest novel strategies for targeting antigens to the activating or inhibitory CD32 expressed on human Dcs to generate either antigen-specific immunity or tolerance.
TITLE: Activating and inhibitory IgG Fc receptors mediate opposing functions on human DCs
AUTHOR CONTACT:
Adam Boruchov
Memorial Sloan-Kettering Cancer Center, New York, NY USA
Phone: 212 639-5187; Fax: 212 937-2467; E-mail: boruchoa@mskcc.org
View the PDF of this article at: https://www.the-jci.org/article.php?id=24772
Journal
Journal of Clinical Investigation