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Scientific article
English

Mouse FcgammaRII is a negative regulator of FcgammaRIII in IgG immune complex-triggered inflammation but not in autoantibody-induced hemolysis

Published inEuropean Journal of Immunology, vol. 30, no. 2, p. 481-490
Publication date2000
Abstract

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.

Keywords
  • Anemia, Hemolytic/genetics/ immunology
  • Animals
  • Antigen-Antibody Complex/immunology
  • Arthus Reaction/genetics/ immunology
  • Autoantibodies/immunology
  • Down-Regulation
  • Gene Expression Regulation/immunology
  • Immunoglobulin G/immunology
  • Mice
  • Mice, Inbred C57BL
  • Receptors, IgG/genetics/ immunology
Affiliation Not a UNIGE publication
Citation (ISO format)
SCHILLER, C. et al. Mouse FcgammaRII is a negative regulator of FcgammaRIII in IgG immune complex-triggered inflammation but not in autoantibody-induced hemolysis. In: European Journal of Immunology, 2000, vol. 30, n° 2, p. 481–490. doi: 10.1002/1521-4141(200002)30:2<481::AID-IMMU481>3.0.CO;2-L
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ISSN of the journal0014-2980
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