Murine IgG1 complexes trigger immune effector functions predominantly via Fc gamma RIII (CD16).
Previously, we have demonstrated that phagocytosis of IgG1-coated particles by macrophages in vitro is impaired by deletion of Fc gamma RIII in mice, suggesting that IgG1 may interact preferentially with Fc gamma RIII. In the present study, the biologic relevance of this observation was addressed by triggering various effector functions of the immune system in Fc gamma RIII(-/-) mice, using panels of mAbs of different IgG subclasses. Both binding and phagocytosis of IgG1-coated sheep or human erythrocytes by Fc gamma RIII(-/-) macrophages in vitro were strongly impaired, indicating that the impaired ingestion of complexed IgG1 by Fc gamma RIII(-/-) macrophages is due to a defect in binding. An in vivo consequence of the defective phagocytosis was observed by resistance of Fc gamma RIII-deficient mice to experimental autoimmune hemolytic anemia, as shown by a lack of IgG1-mediated erythrophagocytosis in vivo by liver macrophages. Furthermore, trapping of soluble IgG1-containing immune complexes by follicular dendritic cells in mesenteric lymph nodes from Fc gamma RIII(-/-) mice was abolished. Whole blood from Fc gamma RIII(-/-) mice was unable to induce lysis of tumor cells in the presence of IgG1 antitumor Abs. Finally, IgG1 mAbs proved unable to mount a passive cutaneous anaphylaxis in Fc gamma RIII(-/-) mice. Together, these results demonstrate that IgG1 complexes, either in particulate or in soluble form, trigger in vitro and in vivo immune effector functions in mice predominantly via Fc gamma RIII.
Hazenbos
W L
WL
Department of Immunology, University Hospital Utrecht, The Netherlands.
Heijnen
I A
IA
Meyer
D
D
Hofhuis
F M
FM
Renardel de Lavalette
C R
CR
Schmidt
R E
RE
Capel
P J
PJ
van de Winkel
J G
JG
Gessner
J E
JE
van den Berg
T K
TK
Verbeek
J S
JS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D001789:Blood Group Antigens / Q000276:immunology; D001943:Breast Neoplasms; D003713:Dendritic Cells / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007106:Immune Sera / Q000502:physiology; D007074:Immunoglobulin G / Q000097:blood / Q000494:pharmacology / Q000502:physiology*; D008099:Liver / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009928:Organ Specificity / Q000276:immunology; D010323:Passive Cutaneous Anaphylaxis; D010587:Phagocytosis / Q000276:immunology; D017452:Receptors, IgG / Q000502:physiology*; D012397:Rosette Formation; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D001789:Blood Group Antigens; D007106:Immune Sera; D007074:Immunoglobulin G; D017452:Receptors, IgG