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 uncertain as serum IgG levels are sufficient to competitively inhibit interactions between this high-affinity receptor and sensitized red cells. In the current study, it is proposed that, rather than functioning as a receptor for opsonized red cells, Fc gamma RI might, under appropriate conditions, mediate the passive sensitization (or 'arming') of human macrophages with IgG antibodies resulting in the in vivo destruction of unsensitized cells expressing the corresponding antigen. To examine this hypothesis, Fc gamma RI-bearing human monocytes and U937 cells were first passively sensitized by incubation in vitro with human monoclonal anti-D, and then incubated with D-positive red cells. The uptake of monoclonal anti-D by U937 cells was rapid and, in the presence of 2.5 micrograms/ml IgG1 or IgG3 anti-D, was almost complete after 5 min at 37 degrees. Subsequent incubation of passively sensitized U937 cells in an IgG-free medium for 1 hr at 37 degrees resulted in the loss from the cell surface of approximately 50% cell-bound IgG; the remaining cell-bound IgG was lost more slowly despite repeated washing. In functional assays, passively sensitized monocytes (M-IgG) mediated adherent, phagocytic and chemiluminescent (CL) responses to D-positive red cells. After incubation of M-IgG in 50% v/v fresh normal human serum (FNHS) for 2 hr, sufficient anti-D remained bound to monocytes to promote the adherence of red cells. The adherence and phagocytosis of red cells by M-IgG was enhanced by the simultaneous addition of 50% FNHS, probably owing to the binding of low levels of C3bi to red cells. In contrast, phagocytic and CL responses of unsensitized monocytes to anti-D-sensitized 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 considered that in vivo, Fc gamma RI may mediate the passive sensitization of macrophages in close proximity with antibody-secreting cells in the reticular network of the splenic cords. Once 'armed' in this way, macrophages may destroy cells expressing the appropriate antigen.
International Blood Group Reference Laboratory, University of Bristol.
H L
HL
Griffiths
B M
BM
Kumpel
C J
CJ
Elson
A G
AG
Hadley
D000911:Antibodies, Monoclonal / Q000276:immunology; D001769:Blood; D016923:Cell Death / Q000276:immunology; D002460:Cell Line; D004912:Erythrocytes; D005434:Flow Cytometry; D006801:Humans; D007116:Immunization, Passive; D007518:Isoantibodies / Q000276:immunology*; D008163:Luminescent Measurements; D009000:Monocytes / Q000276:immunology*; D010587:Phagocytosis; D017452:Receptors, IgG / Q000502:physiology*; D012204:Rh-Hr Blood-Group System; D018029:Rho(D) Immune Globulin
D000911:Antibodies, Monoclonal; D007518:Isoantibodies; C061961:RHO(D) antibody; D017452:Receptors, IgG; D012204:Rh-Hr Blood-Group System; D018029:Rho(D) Immune Globulin