Analyses of the in vivo trafficking of stoichiometric doses of an anti-complement receptor 1/2 monoclonal antibody infused intravenously in mice.
Complement plays a critical role in the immune response by opsonizing immune complexes (IC) and thymus-independent type 2 Ags with C3 breakdown product C3dg, a CR2-specific ligand. We used a C3dg-opsonized IC model, anti-CR1/2 mAb 7G6, to investigate how such substrates are processed. We used RIA, whole body imaging, flow cytometry, and fluorescence immunohistochemistry to examine the disposition of 0.1- to 2-microg quantities of mAb 7G6 infused i.v. into BALB/c mice. The mAb is rapidly taken up by the spleen and binds preferentially to marginal zone (MZ) B cells; within 24 h, the MZ B cells relocate and transfer mAb 7G6 to follicular dendritic cells (FDC). Transfer occurs coincident with loss of the extracellular portion of MZ B cell CR2, suggesting that the process may be mediated by proteolysis of CR2. Intravenous infusion of an FDC-specific mAb does not induce comparable splenic localization or cellular reorganization, emphasizing the importance of MZ B cells in intrasplenic trafficking of bound substrates. We propose the following mechanism: binding of C3dg-opsonized IC to noncognate MZ B cells promotes migration of these cells to the white pulp, followed by CR2 proteolysis, which allows transfer of the opsonized IC to FDC, thus facilitating presentation of intact Ags to cognate B cells.
Department of Biochemistry and Molecular Genetics, University of Virginia, School of Medicine, Charlottesville, VA 22908, USA.
Emily C
EC
Whipple
Ryan S
RS
Shanahan
Andrew H
AH
Ditto
Ronald P
RP
Taylor
Margaret A
MA
Lindorfer
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D017951:Antigen Presentation / Q000276:immunology*; D000936:Antigen-Antibody Complex / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D003179:Complement C3b / Q000276:immunology*; D020566:Dendritic Cells, Follicular / Q000276:immunology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D007262:Infusions, Intravenous; D051379:Mice; D010446:Peptide Fragments / Q000276:immunology*; D011863:Radioimmunoassay; D011951:Receptors, Complement / Q000276:immunology*; D017464:Receptors, Complement 3d / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D010446:Peptide Fragments; D011951:Receptors, Complement; D017464:Receptors, Complement 3d; C045477:complement C3d,g; D003179:Complement C3b