THE FUNCTIONAL-ACTIVITY OF HUMAN MONOCYTES PASSIVELY SENSITIZED WITH MONOCLONAL ANTI-D SUGGESTS A NOVEL ROLE FOR FC-GAMMA-RI IN THE IMMUNE DESTRUCTION OF BLOOD-CELLS

The role of Fc gamma RI in the immune destruction of blood cells is un certain as serum IgG levels are sufficient to competitively inhibit in teractions between this high-affinity receptor and sensitized red cell s. In the current study, it is proposed that, rather than functioning as a receptor for opsonized red cells, Fc gamma RI might, under approp riate conditions, mediate the passive sensitization (or 'arming') of h uman macrophages with IgG antibodies resulting in the in vivo destruct ion of unsensitized cells expressing the corresponding antigen. To exa mine this hypothesis, Fc gamma RI-bearing human monocytes and U937 cel ls were first passively sensitized by incubation in vitro with human m onoclonal anti-D, and then incubated with D-positive red cells. The up take of monoclonal anti-D by U937 cells was rapid and, in the presence of 2.5 mu g/ml IgG1 or IgG3 anti-D, was almost complete after 5 min a t 37 degrees. Subsequent incubation of passively sensitized U937 cells in an IgG-free medium for 1 hr at 37 degrees resulted in the loss fro m the cell surface of approximately 50% cell-bound IgG; the remaining cell-bound IgG was lost more slowly despite repeated washing. In funct ional assays, passively sensitized monocytes (M-IgG) mediated adherent , phagocytic and chemiluminescent (CL) responses to D-positive red cel ls. After incubation of M-IgG in 50% v/v fresh normal human serum (FNH S) for 2 hr, sufficient anti-D remained bound to monocytes to promote the adherence of red cells. The adherence and phagocytosis of red cell s by M-IgG was enhanced by the simultaneous addition of 50% FNHS, prob ably owing to the binding of low levels of C3bi to red cells. In contr ast, phagocytic and CL responses of unsensitized monocytes to anti-D-s ensitized red cells (E-IgG) were abrogated in the presence of 0.25% v/ v FNHS, presumably owing to blocking of Fc gamma RI by IgG. It is cons idered that in vivo, Fc gamma RI may mediate the passive sensitization of macrophages in close proximity with antibody-secreting cells in th e reticular network of the splenic cords. Once 'armed' in this way, ma crophages may destroy cells expressing the appropriate antigen.