Restoration of Tolerance in Lupus by Targeted Inhibitory Receptor Expression.
McGaha, Tracy L. 1; Sorrentino, Brian 2; Ravetch, Jeffrey V. 1*
[Report]
Science.
307(5709):590-593, January 28, 2005.
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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 (Fc[gamma]RIIB) levels on B cells in lupus-prone mouse strains is sufficient to restore tolerance and prevent autoimmunity. Fc[gamma]RIIB 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 Fc[gamma]RIIB levels on B cells may be an effective way to treat autoimmune diseases.
Copyright (C) 2005 by the American Association for the Advancement of Science