Binding and catabolism of aggregated immunoglobulins containing C3b by U937 cells.
We studied Fc receptor and C3b receptor (CR1) function on U937 cells, a human monocyte cell line. C3b was incorporated into stable soluble heat aggregates of 125I-IgM (A-IgM) and 125I-IgG (A-IgG) by using functionally pure classical pathway components. C3b incorporation was verified by the ability of aggregates to bind to human red cells and by cosedimentation of 125I and 131I during ultracentrifugation. Cell uptake and degradation of A-IgG X C3b was increased up to twofold compared with A-IgG not containing C3b molecules. However, A-IgG X C3b bound to CR1 after Fc receptors were blocked with nonradiolabeled A-IgG were also not endocytosed and catabolized. Moreover, A-IgM X C3b was bound but not degraded by U937 cells. As expected, uptake of A-IgM without C3b was negligible. CR1-mediated binding of A-IgM X C3b was specifically inhibited both by a murine monoclonal antibody against the human CR1 that blocks C3b binding and by C3b oligomers generated by trypsin activation of C3, but not by monoclonal antibodies against the iC3b receptor (CR3). We conclude that CR1 on U937 cells cause increased binding of A-IgG, and this increased binding leads to increased Fc-mediated endocytosis and catabolism of model immune complexes. However, binding of soluble ligands by CR1 alone, even when binding is multivalent, does not lead to endocytosis and degradation of soluble ligands bearing C3b.
D000936:Antigen-Antibody Complex / Q000378:metabolism; D002460:Cell Line; D003179:Complement C3b / Q000378:metabolism* / Q000502:physiology; D004705:Endocytosis; D004912:Erythrocytes / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D007075:Immunoglobulin M / Q000378:metabolism*; D046911:Macromolecular Substances; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D009994:Osmolar Concentration; D011951:Receptors, Complement / Q000032:analysis / Q000502:physiology; D017463:Receptors, Complement 3b; D013696:Temperature
D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D046911:Macromolecular Substances; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; C044411:polymeric IgG; C024242:polymeric IgM; D003179:Complement C3b