FcgammaRIIB in autoimmunity and infection: evolutionary and therapeutic implications.
FcgammaRIIB is the only inhibitory Fc receptor. It controls many aspects of immune and inflammatory responses, and variation in the gene encoding this protein has long been associated with susceptibility to autoimmune disease, particularly systemic lupus erythematosus (SLE). FcgammaRIIB is also involved in the complex regulation of defence against infection. A loss-of-function polymorphism in FcgammaRIIB protects against severe malaria, the investigation of which is beginning to clarify the evolutionary pressures that drive ethnic variation in autoimmunity. Our increased understanding of the function of FcgammaRIIB also has potentially far-reaching therapeutic implications, being involved in the mechanism of action of intravenous immunoglobulin, controlling the efficacy of monoclonal antibody therapy and providing a direct therapeutic target.
Smith
Kenneth G C
KG
Cambridge Institute for Medical Research and the Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge CB2 0XY, UK. kgcs2@cam.ac.uk
Clatworthy
Menna R
MR
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D001424:Bacterial Infections / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology; D005786:Gene Expression Regulation; D014644:Genetic Variation; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D008180:Lupus Erythematosus, Systemic / Q000208:ethnology / Q000276:immunology; D008288:Malaria / Q000208:ethnology / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D017452:Receptors, IgG / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*
D016207:Cytokines; C499173:FCGR2B protein, human; D016756:Immunoglobulins, Intravenous; D017452:Receptors, IgG