Research & Development, Canadian Blood Services, Toronto, ON, Canada.
Blood. 2012 May 31;119(22):5261-4. doi: 10.1182/blood-2012-03-415695. Epub 2012 Apr 16.
A recognized paradigm for the therapeutic action of intravenous immunoglobulin (IVIG) in immune thrombocytopenia (ITP) involves up-regulation of the inhibitory Fcγ receptor (FcγRIIB) in splenic macrophages. However, published data have indicated that opposing results are obtained when using FcγRIIB-deficient mice on different strain backgrounds. Herein we show BALB/c FcγRIIB(-/-) and wild-type, with or without spleens, all recover ITP with similar dynamics after IVIG (1 g/kg) treatment; however, this was not the case for C57BL/6 (B6) FcγRIIB(-/-). In investigating this conundrum, we found that wild-type B6 mice are much less sensitive than BALB/c to IVIG-mediated amelioration of ITP, requiring approximately 2- to 2.5-fold more IVIG than BALB/c. When using 2.5 g/kg IVIG in FcγRIIB(-/-) B6 mice, amelioration of ITP was as in wild-type in all animals. Our findings led us to the conclusion that different strains of mice respond differently to IVIG and that FcγRIIB plays no role in the mechanism of effect of IVIG in experimental ITP.
静脉注射免疫球蛋白（IVIG）在免疫性血小板减少症（ITP）中的治疗作用的公认模式涉及脾脏巨噬细胞中抑制性 Fcγ 受体（FcγRIIB）的上调。然而，已发表的数据表明，当使用不同遗传背景的 FcγRIIB 缺陷小鼠时，会得到相反的结果。在此，我们展示了 BALB/c FcγRIIB(-/-)和野生型，无论是否有脾脏，在接受 IVIG（1 g/kg）治疗后，所有 ITP 均以相似的动力学恢复；然而，对于 C57BL/6（B6）FcγRIIB(-/-)则并非如此。在研究这个难题时，我们发现野生型 B6 小鼠对 IVIG 介导的 ITP 改善的敏感性比 BALB/c 低得多，需要大约 2-2.5 倍的 IVIG 才能达到 BALB/c 的效果。当在 FcγRIIB(-/-)B6 小鼠中使用 2.5 g/kg IVIG 时，所有动物的 ITP 改善均与野生型相同。我们的研究结果得出结论，不同品系的小鼠对 IVIG 的反应不同，并且 FcγRIIB 不参与 IVIG 在实验性 ITP 中的作用机制。
