期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2012
卷号：109
期号：16
页码：6181-6186
DOI：10.1073/pnas.1203954109
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The in vivo biological activities of IgG antibodies result from their bifunctional nature, in which antigen recognition by the Fab is coupled to the effector and immunomodulatory diversity found in the Fc domain. This diversity, resulting from both amino acid and glycan heterogeneity, is translated into cellular responses through Fc{gamma} receptors (Fc{gamma}Rs), a structurally and functionally diverse family of cell surface receptors found throughout the immune system. Although many of the overall features of this system are maintained throughout mammalian evolution, species diversity has precluded direct analysis of human antibodies in animal species, and, thus, detailed investigations into the unique features of the human IgG antibodies and their Fc{gamma}Rs have been limited. We now report the development of a mouse model in which all murine Fc{gamma}Rs have been deleted and human Fc{gamma}Rs, encoded as transgenes, have been inserted into the mouse genome resulting in recapitulation of the unique profile of human Fc{gamma}R expression. These human Fc{gamma}Rs are shown to function to mediate the immunomodulatory, inflammatory, and cytotoxic activities of human IgG antibodies and Fc engineered variants and provide a platform for the detailed mechanistic analysis of therapeutic and pathogenic IgG antibodies.
