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Differential contribution of three activating IgG Fc receptors (FcgammaRI, FcgammaRIII, and FcgammaRIV) to IgG2a- and IgG2b-induced autoimmune hemolytic anemia in mice

机译:三种激活的IgG Fc受体(FcgammaRI,FcgammaRIII和FcgammaRIV)对IgG2a和IgG2b诱导的小鼠自身免疫性溶血性贫血的不同贡献

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摘要

Murine phagocytes express three different activating IgG FcgammaR: FcgammaRI is specific for IgG2a; FcgammaRIII for IgG1, IgG2a, and IgG2b; and FcgammaRIV for IgG2a and IgG2b. Although the role of FcgammaRIII in IgG1 and IgG2a anti-RBC-induced autoimmune hemolytic anemia (AIHA) is well documented, the contribution of FcgammaRI and FcgammaRIV to the development of IgG2a- and IgG2b-induced anemia has not yet been defined. In the present study, using mice deficient in FcgammaRI, FcgammaRIII, and C3, in combination with an FcgammaRIV-blocking mAb, we assessed the respective roles of these three FcgammaR in the development of mild and severe AIHA induced by two different doses (50 and 200 microg) of the IgG2a and IgG2b subclasses of the 34-3C anti-RBC monoclonal autoantibody. We observed that the development of mild anemia induced by a low dose of 34-3C IgG2a autoantibody was highly dependent on FcgammaRIII, while FcgammaRI and FcgammaRIV additionally contributed to the development of severe anemia induced by a high dose of this subclass. In contrast, the development of both mild and severe anemia induced by 34-3C IgG2b was dependent on FcgammaRIII and FcgammaRIV. Our results indicate differential roles of the three activating FcgammaR in IgG2a- and IgG2b-mediated AIHA.
机译:鼠吞噬细胞表达三种不同的活化IgG FcgammaR:FcgammaRI对IgG2a具有特异性; IgG1,IgG2a和IgG2b的FcγRIII;以及IgG2a和IgG2b的FcgammaRIV。尽管FcgammaRIII在IgG1和IgG2a抗RBC诱导的自身免疫性溶血性贫血(AIHA)中的作用已有充分文献记载,但尚未确定FcgammaRI和FcgammaRIV对IgG2a和IgG2b诱导的贫血发展的贡献。在本研究中,使用FcgammaRI,FcgammaRIII和C3缺陷的小鼠与FcgammaRIV阻断性mAb结合,我们评估了这三种FcgammaR在两种不同剂量诱导的轻度和重度AIHA发生中的各自作用(50和200微克)的34-3C抗RBC单克隆自身抗体的IgG2a和IgG2b亚类。我们观察到由低剂量的34-3C IgG2a自身抗体诱导的轻度贫血的发生高度依赖于FcgammaRIII,而FcgammaRI和FcgammaRIV额外导致了由高剂量的该亚类引起的严重贫血的发生。相反,由34-3C IgG2b诱导的轻度和重度贫血的发生均取决于FcgammaRIII和FcgammaRIV。我们的结果表明三种活化FcgammaR在IgG2a和IgG2b介导的AIHA中的不同作用。

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