Mouse FcgammaRII is a negative regulator of FcgammaRIII in IgG immune complex-triggered inflammation but not in autoantibody-induced hemolysis.
Murine low-affinity receptors for IgG, FcgammaRII and FcgammaRIII, differ by their distinct capacities in mediating down-regulation or activation of cellular effector functions, respectively. In this study, antibodies detecting the mouse Ly-17.1 / 2 alloantigen system are demonstrated to be specific for FcgammaRII with no cross-reactivities to other FcgammaR, including FcgammaRIII. Using these FcgammaRII-specific monoclonal antibodies (mAb), the significance of FcgammaRII inhibition of FcgammaRIII was examined in two models of autoantibody [autoimmune hemolytic anemia (AIHA)]- and IgG immune complex-induced (Arthus reaction) inflammation in C57BL / 6 mice in comparison with FcgammaRII(- / -) and FcgammaRIII(- / -) mice. Our results demonstrate that both FcgammaRIII and FcgammaRII contributed to the binding of erythrocytes opsonized with the pathogenic IgG1 autoreactive anti-murine red blood cell antibody 105-2H. However, the functional blocking with anti-FcgammaRII mAb in C57BL / 6 mice and the lack of FcgammaRII expression in FcgammaRII(- / -) mice, which both lowered the threshold level of FcgammaRIII-triggered phagocytosis in vitro, did not results in enhanced disease development of 105-2H mAb-induced AIHA in vivo. This was in sharp contrast to cutaneous Arthus reaction, where FcgammaRIII-mediated activation was inhibited by FcgammaRII. Together these results show that murine AIHA is markedly different from other FcgammaR-dependent inflammatory diseases where FcgammaRIII is normally counterregulated by FcgammaRII.
Schiller
C
C
Department of Clinical Immunology Medical School Hannover, Hannover, Germany.
Janssen-Graalfs
I
I
Baumann
U
U
Schwerter-Strumpf
K
K
Izui
S
S
Takai
T
T
Schmidt
R E
RE
Gessner
J E
JE
D000743:Anemia, Hemolytic / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology; D001183:Arthus Reaction / Q000235:genetics / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology*
D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D007074:Immunoglobulin G; D017452:Receptors, IgG