title: Clearance of anti-double-stranded DNA antibodies: the natural immune complex clearance mechanism.
abstract: OBJECTIVE
  To develop an in vitro model for investigating the mechanism by which autoantibodies in immune complexes (ICs) that are bound to primate erythrocytes via antigen-based heteropolymers (AHPs) are cleared from the circulation and localized to the liver.
  
  
  METHODS
  IgG anti-double-stranded DNA (anti-dsDNA) antibodies in ICs with dsDNA were bound to human erythrocytes via complement receptor 1 (CR1) either by opsonization with normal human serum as a complement source or through the use of an AHP, which consists of an anti-CR1 monoclonal antibody (mAb) that is chemically crosslinked with dsDNA. We performed parallel investigations of the mechanism of transfer of both types of erythrocyte-bound ICs to a monocytic cell line (U937). Erythrocytes with CR1-bound ICs were incubated with U937 cells under a variety of conditions, and subsequently, the levels of IgG anti-dsDNA, CR1, AHP, or C3b on both erythrocytes and U937 cells were measured by flow cytometry with appropriate fluorescently labeled probes.
  
  
  RESULTS
  In the presence of U937 cells, both the AHP-anti-dsDNA and C3b-opsonized ICs were rapidly removed from the erythrocytes; at 37 degrees C, more than half of the complexes were removed in 2 minutes. Monomeric mouse IgG2a mAb blocked the transfer of both types of complexes by 75%, suggesting that Fcgamma receptor type I (FcgammaRI) is the main phagocyte receptor responsible for the removal of ICs from erythrocytes. Levels of CR1 on the erythrocyte surface were reduced during transfer of the AHP-anti-dsDNA ICs, suggesting that transfer involves a concomitant removal of CR1, presumably by proteolysis.
  
  
  CONCLUSIONS
  Transfer of AHP-anti-dsDNA ICs from erythrocyte CR1 to model phagocytes occurs by a mechanism that is similar to the natural mechanism of IC clearance, involving recognition by FcgammaRI and removal of erythrocyte CR1 as key steps.
authors.affiliation: University of Virginia School of Medicine, Charlottesville, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Craig
authors.forename: A J
authors.initials: AJ
authors.lastname: Bankovich
authors.forename: J L
authors.initials: JL
authors.lastname: McElhenny
authors.forename: R P
authors.initials: RP
authors.lastname: Taylor
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000378:metabolism*; D000936:Antigen-Antibody Complex / Q000187:drug effects / Q000378:metabolism; D001327:Autoimmune Diseases / Q000378:metabolism; D004247:DNA / Q000276:immunology*; D004912:Erythrocytes / Q000737:chemistry / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors; D051379:Mice; D010586:Phagocytes / Q000276:immunology; D017463:Receptors, Complement 3b / Q000276:immunology; D020298:U937 Cells
chemical_list: D000974:Antibodies, Antinuclear; D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D017463:Receptors, Complement 3b; D004247:DNA; D008666:Metalloendopeptidases