Restoration of tolerance in lupus by targeted inhibitory receptor expression.
Lupus, a multigenic autoimmune condition in which a breakdown of tolerance results in the development of autoantibodies, leads to a variety of pathologic outcomes. Despite the heterogeneity of factors influencing disease susceptibility, we demonstrate that the partial restoration of inhibitory Fc receptor (FcgRIIB) levels on B cells in lupus-prone mouse strains is sufficient to restore tolerance and prevent autoimmunity. FcgRIIB regulates a common B cell checkpoint in genetically diverse lupus-prone mouse strains, and modest changes in its expression can result in either tolerance or autoimmunity. Therefore, increasing FcgammaRIIB levels on B cells may be an effective way to treat autoimmune diseases.
McGaha
Tracy L
TL
Laboratory of Molecular Genetics and Immunology, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
Sorrentino
Brian
B
Ravetch
Jeffrey V
JV
D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D001323:Autoantibodies / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology*; D016026:Bone Marrow Transplantation; D002843:Chromatin / Q000276:immunology; D005260:Female; D005822:Genetic Vectors; D007668:Kidney / Q000473:pathology; D008168:Lung / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000276:immunology; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism*; D012190:Retroviridae / Q000235:genetics; D017634:Self Tolerance; D013601:T-Lymphocytes / Q000276:immunology; D014161:Transduction, Genetic
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D002843:Chromatin; C499172:Fcgr2b protein, mouse; D017452:Receptors, IgG