Clearance of immune complexes by the mononuclear phagocyte system is important for maintaining normal host defenses against bacterial and viral assault (1), but also contributes to the pathogenesis of a variety of immune-mediated diseases . For example, removal from the circulation of IgG-coated erythrocytes and platelets by the MPS is the sine qua non of immune-mediated cytopenias (2, 3). On the other hand, abnormally decreased removal by the MPS of smaller, soluble immune complexes may play a role in the pathogenesis of immune complex-mediated tissue damage found in such autoimmune diseases as SLE (4).Although the physicochemical nature and the size of immune complexes can influence rates of clearance and sites of deposition (reviewed in 5), interactions between immune complexes and the MPS in vivo are poorly understood . The inability to directly measure binding or internalization of immune complexes by cells in the liver and spleen has made the analysis of the molecular basis of immune complex clearance very difficult . Receptors for the Fc portion of IgG (FcyR) and for complement (CR) undoubtedly play a role in the removal of immune complexes, but the relative importance of these receptors is not known.There are three types of FcyRs on human leukocytes . A 72 kD receptor with high affinity for monomeric IgG is found on monocytes (6) and some resident macrophages (7). Two receptors exist with low affinity for monomeric IgG, one with broad electrophoretic mobility (51-73 kD) on neutrophils (8), natural killer cells (9), and macrophages (8); the other recently described (40 kD) on platelets (10), monocytes (10), and several tumor cell lines (11). All three bind immunoglobulin that is aggregated or complexed to antigen . The 51-73 kD receptor is recognized by mAb 3G8, which blocks ligand binding and has been very useful in the partial biochemical characterization of this receptor (8).In vitro analysis of the role played by FcyRs in individuals with abnormally prolonged clearance of opsonized red cells (model particulate immune complexes) generally has been limited to studies of high-affinity FcyRs on monocytes.

Our laboratory has focused on the structure and function of the murine dendritic cell (DC; 1). 1 This lymphoid element has a characteristic structure and surface topography and represents a minor population of the cells (1% or less) released from dissociated spleen and lymph node. DC can be purified, and by cytologic criteria they are >90% pure. Purified DC exhibited unique functional properties. They are the most potent stimulators of the allogeneic and syngeneic mixed leukocyte reactions (2, 3) and act as accessory cells in proliferative and cytotoxic T cell responses (4-7).Cell surface markers have contributed to the characterization of spleen DC. Initially it was noted that DC lacked surface immunoglobulin (Ig), brain antigen (Ag), Thy-1 Ag, and Fc and C3 receptors (8). These markers set DC apart from macrophages (Mth) and lymphocytes, particularly when combined with such other differences as distinctive morphology, steroid and radiosensitivity, rapid turnover, weak endocytic activity, and distribution in situ (9). The lack of Fc receptors was useful in purifying DC from DC-Mth mixtures (10). Purified DC all expressed Ia Ag, and did not acquire the surface markers of Mq~ or lymphocytes when cultured in vitro for several days. Further analysis of the cell surface should facilitate the identification of DC in complex cell mixtures, help outline its lineage, and explain its functional capacities.We have therefore performed a detailed study comparing the surface of DC with other bone marrow-derived elements. Monoclonal antibodies and lactoperoxidasemediated surface iodination provided sensitive quantitative and biochemical information. The data show that spleen DC constitutively express high levels of Ia and H-2D alloantigens. DC carry the leukocyte common antigen, but can be distinguished from other leukocytes by several surface markers detected with monoclonal antibodies. Our findings indicate that spleen DC are part of a distinct, Ia-rich, leukocyte differentiation pathway.

We used soluble, C-fixing antibody/dsDNA IC to investigate immune complex (IC) handling and erythrocyte (E)-to-phagocyte transfer in chimpanzees. IC bound efficiently to chimpanzee E in vitro and showed minimal release with further in vitro incubation in the presence of serum in EDTA (c 15% within 1 h). These IC also bound rapidly to E in vivo (70-80% binding within 1 min) and did not show detectable release from E in the peripheral circulation after infusion in vivo (< 2% within 1 h). Despite such slow C-mediated release of IC from E, IC were rapidly stripped from E by the mononuclear phagocyte system (T50 for E-IC1500 = 5 min) without sequestration of E.