EA2216 Immunology and Pathology and Institut Fédératif de Recherche 148, Université de Bretagne Occidentale, Brest, France.
Blood. 2010 Sep 9;116(10):1698-704. doi: 10.1182/blood-2009-12-261461. Epub 2010 Jun 1.
Among various mechanisms for interactions with B cells, intravenous immunoglobulin (IVIg) may operate through the insertion of its Fc part into the Fc-γ receptor, or the binding of its sialic acid (SA)-bearing glycans to the negatively regulating CD22 lectin. It appeared that IVIg reduces B lymphocyte viability in a dose- and time-dependent manner. Furthermore, we show by confocal microscopy that SA-positive IgG, but not SA-negative IgG bind to CD22. This interaction reduces the strength of B-cell receptor-mediated signaling trough down-regulating tyrosine phosphorylation of Lyn and the B-cell linker proteins, and up-regulating phospholipase Cγ2 activation. This cascade resulted in a sustained activation of Erk 1/2 and arrest of the cell cycle at the G(1) phase. These changes may be accounted for the efficacy of IVIg in autoimmune diseases.
在与 B 细胞相互作用的各种机制中，静脉注射免疫球蛋白（IVIg）可能通过将其 Fc 部分插入 Fc-γ 受体，或其带有唾液酸（SA）的聚糖与负调节 CD22 凝集素结合来发挥作用。似乎 IVIg 以剂量和时间依赖的方式降低 B 淋巴细胞的活力。此外，我们通过共聚焦显微镜显示，SA 阳性 IgG，但不是 SA 阴性 IgG 与 CD22 结合。这种相互作用通过下调 Lyn 和 B 细胞连接蛋白的酪氨酸磷酸化以及上调磷脂酶 Cγ2 的激活，来降低 B 细胞受体介导的信号转导强度。这种级联反应导致 Erk1/2 的持续激活和细胞周期停滞在 G1 期。这些变化可能解释了 IVIg 在自身免疫性疾病中的疗效。
