Heterogeneity of Human IgG Fc Receptors

The complex family of human IgG Fc receptors show a wide cellular distribution and a strong functional heterogeneity. To date, eight different genes that are transcribed into at least 12 different mRNAs have been recognized. Although corresponding products have been identified for only some of the transcripts, in vivo at least six different FcγR isoforms are shown to be present on the surface of all kinds of leukocytes. Upon interaction with immunoglobulin, FcγR mediate a variety of biological responses such as phagocytosis, endocytosis, release of inflammatory mediators, and antibody-dependent cellular cytotoxicity. One of the main questions in FcγR research is determining the specific relationship between a particular FcγR isoform and a particular effector mechanism. The availability of the cDNA and genomic clones corresponding to the different isoforms, combined with different gene transfer systems in vitro and in vivo and the recently developed procedure of gene knockout by homologous recombination, allows the generation of stably transfected cell lines and transgenic animals that express one particular FcγR isoform. These model systems enable us to study the function of a particular FcγR isoform in the context of a particular cell type in vitro and in the context of the intact immune system in vivo.