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

Schiller, C.
Janssen-Graalfs, I.
Baumann, U.
Schwerter-Strumpf, K.
Takai, T.
Schmidt, R. E.
Gessner, J. E.
Published in European Journal of Immunology. 2000, vol. 30, no. 2, p. 481-490
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/ immunologyAnimalsAntigen-Antibody Complex/immunologyArthus Reaction/genetics/ immunologyAutoantibodies/immunologyDown-RegulationGene Expression Regulation/immunologyImmunoglobulin G/immunologyMiceMice, Inbred C57BLReceptors, IgG/genetics/ immunology
PMID: 10671203
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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.

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Deposited on : 2010-08-27

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