HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Baudino, L. Articles by Izui, S. Search for Related Content PubMed PubMed Citation Articles by Baudino, L. Articles by Izui, S.

Differential Contribution of Three Activating IgG Fc Receptors (FcRI, FcRIII, and FcRIV) to IgG2a- and IgG2b-Induced Autoimmune Hemolytic Anemia in Mice¹

Lucie Baudino^*, Falk Nimmerjahn, Samareh Azeredo da Silveira^*, Eduardo Martinez-Soria^*, Takashi Saito, Michael Carroll, Jeffrey V. Ravetch^¶, J. Sjef Verbeek^|| and Shozo Izui^2,*

^* Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland; Laboratory for Experimental Immunology and Immunotherapy, Nikolaus-Fiebiger-Center for Molecular Medicine, University of Erlangen-Nuremberg, Erlangen, Germany; Laboratory for Cell Signaling, Institute of Physical and Chemical Research Center for Allergy and Immunology, Yokohama, Japan; Center for Blood Research and Department of Pathology, Harvard Medical School, Boston, MA 02115; ^¶ The Rockefeller University, New York, NY 10065; and ^|| Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands

Murine phagocytes express three different activating IgG FcR: FcRI is specific for IgG2a; FcRIII for IgG1, IgG2a, and IgG2b; and FcRIV for IgG2a and IgG2b. Although the role of FcRIII in IgG1 and IgG2a anti-RBC-induced autoimmune hemolytic anemia (AIHA) is well documented, the contribution of FcRI and FcRIV to the development of IgG2a- and IgG2b-induced anemia has not yet been defined. In the present study, using mice deficient in FcRI, FcRIII, and C3, in combination with an FcRIV-blocking mAb, we assessed the respective roles of these three FcR in the development of mild and severe AIHA induced by two different doses (50 and 200 µg) of the IgG2a and IgG2b subclasses of the 34-3C anti-RBC monoclonal autoantibody. We observed that the development of mild anemia induced by a low dose of 34-3C IgG2a autoantibody was highly dependent on FcRIII, while FcRI and FcRIV additionally contributed to the development of severe anemia induced by a high dose of this subclass. In contrast, the development of both mild and severe anemia induced by 34-3C IgG2b was dependent on FcRIII and FcRIV. Our results indicate differential roles of the three activating FcR in IgG2a- and IgG2b-mediated AIHA.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by a grant from the Swiss National Foundation for Scientific Research.

² Address correspondence and reprint requests to Dr. Shozo Izui, Department of Pathology and Immunology, Centre Médicale Universitaire, 1211 Geneva 4, Switzerland. E-mail address: Shozo.Izui{at}medecine.unige.ch

³ Abbreviations used in this paper: NZB, New Zealand Black; AIHA, autoimmune hemolytic anemia; CR, complement receptor; B6, C57BL/6; WT, wild type; Ht, hematocrit.

This article has been cited by other articles:

				A. Giorgini, H. J. Brown, H. R. Lock, F. Nimmerjahn, J. V. Ravetch, J. S. Verbeek, S. H. Sacks, and M. G. Robson Fc{gamma}RIII and Fc{gamma}RIV Are Indispensable for Acute Glomerular Inflammation Induced by Switch Variant Monoclonal Antibodies J. Immunol., December 15, 2008; 181(12): 8745 - 8752. [Abstract] [Full Text] [PDF]

				P. V. Beum, D. A. Mack, A. W. Pawluczkowycz, M. A. Lindorfer, and R. P. Taylor Binding of Rituximab, Trastuzumab, Cetuximab, or mAb T101 to Cancer Cells Promotes Trogocytosis Mediated by THP-1 Cells and Monocytes J. Immunol., December 1, 2008; 181(11): 8120 - 8132. [Abstract] [Full Text] [PDF]

				M. A. Otten, G. J. van der Bij, S. J. Verbeek, F. Nimmerjahn, J. V. Ravetch, R. H. J. Beelen, J. G. J. van de Winkel, and M. van Egmond Experimental Antibody Therapy of Liver Metastases Reveals Functional Redundancy between Fc{gamma}RI and Fc{gamma}RIV J. Immunol., November 15, 2008; 181(10): 6829 - 6836. [Abstract] [Full Text] [PDF]

				L. Baudino, Y. Shinohara, F. Nimmerjahn, J.-I. Furukawa, M. Nakata, E. Martinez-Soria, F. Petry, J. V. Ravetch, S.-I. Nishimura, and S. Izui Crucial Role of Aspartic Acid at Position 265 in the CH2 Domain for Murine IgG2a and IgG2b Fc-Associated Effector Functions J. Immunol., November 1, 2008; 181(9): 6664 - 6669. [Abstract] [Full Text] [PDF]

				H. Albert, M. Collin, D. Dudziak, J. V. Ravetch, and F. Nimmerjahn In vivo enzymatic modulation of IgG glycosylation inhibits autoimmune disease in an IgG subclass-dependent manner PNAS, September 30, 2008; 105(39): 15005 - 15009. [Abstract] [Full Text] [PDF]

				L. Baudino, F. Nimmerjahn, Y. Shinohara, J.-I. Furukawa, F. Petry, J. S. Verbeek, S.-I. Nishimura, J. V. Ravetch, and S. Izui Impact of a Three Amino Acid Deletion in the CH2 Domain of Murine IgG1 on Fc-Associated Effector Functions J. Immunol., September 15, 2008; 181(6): 4107 - 4112. [Abstract] [Full Text] [PDF]