Visualization of the transfer reaction: tracking immune complexes from erythrocyte complement receptor 1 to macrophages.

Immune complexes (IC) bound to human erythrocytes (E) via complement receptor 1 (CR1) are transferred to phagocytes in the liver and spleen. In an in vitro model system using bispecific mAb reagents (antigen-based heteropolymers) to link IC to E, we have made time-lapse movies in which fluorescently labeled IC cross the E-human macrophage interface and remain associated with the macrophage. Both these movies and fixed-time experiments reveal transfer intermediates in which IC hinge E to macrophages. Examination of model macrophages after transfer indicates that the majority of IC are on the surface at short times (2 min) but are internalized at long times (1-4 h). More than half of the surface IC colocalize with CR1 at 2 min. This evidence supports a model in which CR1-bound IC provide a secure linkage between E and macrophages, allowing rearrangements of the macrophage surface necessary for release of CR1, and IC, from the E.