Antibody Responses in Transgenic Mice

Besides their phagocytic effector functions, myeloid cells have an essential role as accessory cells in the induction of optimal humoral immune responses by presenting captured antigens and activating lymphocytes. Antigen presentation by human monocytes was recently found to be enhanced in vitro through the high-affinity Fc receptor for IgG (Fc g RI; CD64), which is exclusively present on myeloid cells. To evaluate a comparable role of Fc g RI in antigen presentation in vivo, we generated human Fc g RI transgenic mice. Under control of its endogenous promoter, human Fc g RI was selectively expressed on murine myeloid cells at physiological expression levels. As in humans, expression was properly regulated by the cytokines IFNg , G-CSF, IL-4, and IL-10, and was up-regulated during inflammation. The human receptor expressed by murine macrophages bound monomeric human IgG and mediated particle phagocytosis and IgG complex internalization. To evaluate whether specific targeting of antigens to Fc g RI can induce enhanced antibody responses, mice were immunized with an anti– human Fc g RI antibody containing antigenic determinants. Transgenic mice produced antigen-specific antibody responses with high IgG1 titers and substantial IgG2a and IgG2b responses. These data demonstrate that human Fc g RI on myeloid cells is highly active in mediating enhanced antigen presentation in vivo, and show that antiFc g RI mAbs are promising vaccine adjuvants. ( J. Clin. Invest. 1996. 97:331 – 338 . )