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Science 307 (5709): 590-593

Copyright © 2005 by the American Association for the Advancement of Science

Restoration of Tolerance in Lupus by Targeted Inhibitory Receptor Expression

Tracy L. McGaha,1 Brian Sorrentino,2 Jeffrey V. Ravetch1*

Abstract: 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 Fc{gamma}RIIB levels on B cells may be an effective way to treat autoimmune diseases.

1 Laboratory of Molecular Genetics and Immunology, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
2 St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38105, USA.

* To whom correspondence should be addressed. E-mail: ravetch{at}rockefeller.edu


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