IVIg modulates BCR signaling through CD22 and promotes apoptosis in mature human B lymphocytes
IVIg modulates BCR signaling through CD22 and promotes apoptosis in mature human B lymphocytes
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DOI：
10.1182/blood-2009-12-261461
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发表时间：
2010-09-09
期刊：
影响因子：
20.3
通讯作者：
Hillion, Sophie
中科院分区：
文献类型：
--
作者：
Seite, Jean-Francois;Cornec, Divi;Hillion, Sophie
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受体或将其唾液酸（SA）承载的聚糖与负调节的CD22凝集素结合而起作用。IVIg似乎以剂量和时间依赖的方式降低B淋巴细胞活力。此外，我们通过共聚焦显微镜发现sa阳性IgG与CD22结合，而sa阴性IgG与CD22不结合。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和上调磷脂酶C γ 2激活来降低b细胞受体介导的信号传导强度。这个级联导致Erk 1/2的持续激活和细胞周期阻滞在G(1)期。这些变化可能解释了IVIg在自身免疫性疾病中的疗效。[血液。2010;116(10):1698-1704]
Among various mechanisms for interactions with B cells, intravenous immunoglobulin (IVIg) may operate through the insertion of its Fc part into the Fc-gamma 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 C gamma 2 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. (Blood. 2010; 116(10):1698-1704)