Mouse and human FcR effector functions

Mouse and human FcRs have been a major focus of attention not only of the scientific community, through the cloning and characterization of novel receptors, and of the medical community, through the identification of polymorphisms and linkage to disease but also of the pharmaceutical community, through the identification of FcRs as targets for therapy or engineering of Fc domains for the generation of enhanced therapeutic antibodies. The availability of knockout mouse lines for every single mouse FcR, of multiple or cell-specifica la carte'FcR knockouts and the increasing generation of hFcR transgenics enable powerful invivo approaches for the study of mouse and human FcR biology. Thisreview will present the landscape of the current FcR family, their effector functions and the invivo models at hand to study them. These invivo models were recently instrumental in re-defining the properties and effector functions of FcRs that had been overlooked or discarded from previous analyses. A particular focus willbe made on the (mis)concepts on the role of high-affinity IgGreceptors invivo and on results from antibody engineering toenhance or abrogate antibody effector functions mediated by FcRs.