Complement activation selectively potentiates the pathogenicity of the IgG2b and IgG3 isotypes of a high affinity anti-erythrocyte autoantibody

The Journal of Experimental Medicine
Samareh Azeredo da SilveiraS Izui

Abstract

By generating four IgG isotype-switch variants of the high affinity 34-3C anti-erythrocyte autoantibody, and comparing them to the IgG variants of the low affinity 4C8 anti-erythrocyte autoantibody that we have previously studied, we evaluated in this study how high affinity binding to erythrocytes influences the pathogenicity of each IgG isotype in relation to the respective contributions of Fcgamma receptor (FcgammaR) and complement. The 34-3C autoantibody opsonizing extensively circulating erythrocytes efficiently activated complement in vivo (IgG2a = IgG2b > IgG3), except for the IgG1 isotype, while the 4C8 IgG autoantibody failed to activate complement. The pathogenicity of the 34-3C autoantibody of IgG2b and IgG3 isotypes was dramatically higher (>200-fold) than that of the corresponding isotypes of the 4C8 antibody. This enhanced activity was highly (IgG2b) or totally (IgG3) dependent on complement. In contrast, erythrocyte-binding affinities only played a minor role in in vivo hemolytic activities of the IgG1 and IgG2a isotypes of 34-3C and 4C8 antibodies, where complement was not or only partially involved, respectively. The remarkably different capacities of four different IgG isotypes of low and high affinity anti-er...Continue Reading

References

Dec 1, 1975·The Journal of Experimental Medicine·J C Unkeless, H N Eisen
Jan 11, 1988·Nucleic Acids Research·T Simon, K Rajewsky
Feb 1, 1971·The Journal of Experimental Medicine·H M GreyM Cohn
Mar 1, 1981·The Journal of Experimental Medicine·B Diamond, D E Yelton
Dec 1, 1981·European Journal of Immunology·M S Neuberger, K Rajewsky
Jul 1, 1995·Immunity·R Clynes, J V Ravetch
Aug 26, 1994·Cell·J V Ravetch
Sep 20, 1996·Science·C R BozicN P Gerard
Dec 1, 1996·The Journal of Experimental Medicine·D SylvestreJ V Ravetch
Jan 13, 1998·Nature Genetics·D GarrickE Whitelaw
Sep 17, 1998·The Journal of Clinical Investigation·S Y ParkT Saito
Dec 10, 1999·The Journal of Experimental Medicine·L Fossati-JimackS Izui
Jan 7, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·U BaumannJ E Gessner

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Citations

Sep 15, 2006·Springer Seminars in Immunopathology·Sachiko HiroseToshikazu Shirai
Sep 6, 2006·Springer Seminars in Immunopathology·Lucie BaudinoShozo Izui
Nov 23, 2006·Springer Seminars in Immunopathology·Falk Nimmerjahn
Nov 11, 2006·Springer Seminars in Immunopathology·Lydie CassardCatherine Sautès-Fridman
Jun 23, 2006·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Joo Hoon LeeYong Choi
Dec 8, 2007·Nature Reviews. Immunology·Falk Nimmerjahn, Jeffrey V Ravetch
Feb 16, 2013·Nature Reviews. Immunology·Inessa Schwab, Falk Nimmerjahn
May 7, 2003·The Journal of Experimental Medicine·Teresita Díaz de StåhlBirgitta Heyman
Nov 20, 2002·The Journal of Clinical Investigation·Lydie CassardCatherine Sautès-Fridman
Feb 3, 2006·The Journal of Clinical Investigation·Varsha KumarJ Engelbert Gessner
Feb 3, 2006·The Journal of Clinical Investigation·John P Atkinson
Feb 5, 2003·Proceedings of the National Academy of Sciences of the United States of America·Frédérique BardTed Yednock
Feb 3, 2012·Cancer Immunology, Immunotherapy : CII·Ravindra A De SilvaPeter R Andreana
Apr 30, 2014·Seminars in Immunopathology·Daniela KaoFalk Nimmerjahn
Mar 15, 2011·Transfusion clinique et biologique : journal de la Société française de transfusion sanguine·M Desmarets, F Noizat-Pirenne
Oct 23, 2009·Journal of Autoimmunity·Marie-Laure Santiago-RaberShozo Izui
Nov 25, 2005·Scandinavian Journal of Immunology·F HjelmB Heyman
Aug 1, 2009·Arthritis and Rheumatism·Marie-Laure Santiago-RaberShozo Izui
Aug 19, 2006·Parasite Immunology·R S McIntoshR J Pleass
Jul 20, 2010·Immunological Reviews·Falk Nimmerjahn, Jeffrey V Ravetch
Oct 26, 2005·Journal of Autoimmunity·D Stahl, W Sibrowski
Sep 30, 2015·Immunity, Inflammation and Disease·Georgios SogkasJohannes Engelbert Gessner
Jul 26, 2005·Immunity·Falk NimmerjahnJeffrey V Ravetch
Apr 11, 2015·Frontiers in Immunology·Florencia Paula Madorsky RowdoJosé Mordoh

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Methods Mentioned

BETA
PCR
ELISA
flow cytometry

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