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Science 313 (5787): 670-673

Copyright © 2006 by the American Association for the Advancement of Science

Anti-Inflammatory Activity of Immunoglobulin G Resulting from Fc Sialylation

Yoshikatsu Kaneko,* Falk Nimmerjahn,* Jeffrey V. Ravetch{dagger}

Abstract: Immunoglobulin G (IgG) mediates pro- and anti-inflammatory activities through the engagement of its Fc fragment (Fc) with distinct Fcg receptors (FcgRs). One class of Fc-FcgR interactions generates pro-inflammatory effects of immune complexes and cytotoxic antibodies. In contrast, therapeutic intravenous gamma globulin and its Fc fragments are anti-inflammatory. We show here that these distinct properties of the IgG Fc result from differential sialylation of the Fc core polysaccharide. IgG acquires anti-inflammatory properties upon Fc sialylation, which is reduced upon the induction of an antigen-specific immune response. This differential sialylation may provide a switch from innate anti-inflammatory activity in the steady state to generating adaptive pro-inflammatory effects upon antigenic challenge.

Laboratory of Molecular Genetics and Immunology, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.

* These authors contributed equally to this work.

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

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