Internalization of B cell receptors in human EU12 μHC⁺ immature B cells specifically alters downstream signaling events.
Internalization of B cell receptors in human EU12 μHC⁺ immature B cells specifically alters downstream signaling events.
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人 EU12 μHC– 未成熟 B 细胞中 B 细胞受体的内化会特异性地改变下游信号事件。
DOI：
10.1155/2013/807240
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发表时间：
2013
影响因子：
--
通讯作者：
Zhang,Zhixin
中科院分区：
文献类型：
--
作者：
Liu,Jing;Xie,Wanqin;Lange,MilesD;Hong,SangYong;Su,Kaihong;Zhang,Zhixin
人们很早就认识到，B 细胞抗原受体 (BCR) 与未成熟 B 细胞或成熟 B 细胞的结合会导致完全相反的细胞命运决定。其根本机制仍不清楚。在这里，我们表明 BCR 在人 EU12μHC+ 未成熟 B 细胞上的交联导致细胞表面 BCR 的完全内化。细胞表面 BCR 丢失后，EU12μHC+ 细胞的再刺激显示 Ca2+ 通量受损、SYK 磷酸化延迟以及 CD19 和 FOXO1 磷酸化降低，这与 BCR 部分内化的成熟 Daudi 或 Ramos B 细胞不同。相反，在 BCR 内化后，在 EU12μHC+ 细胞中观察到再刺激时 ERK 持续磷酸化和重新激活。总而言之，这些结果表明 EU12μHC+ 细胞中细胞表面 BCR 的完全内化特异性地改变了下游信号传导事件，这可能有利于受体编辑而不是细胞激活。
It has been recognized for a long time that engagement of B cell antigen receptors (BCRs) on immature B cells or mature B cells leads to completely opposite cell fate decisions. The underlying mechanism remains unclear. Here, we show that crosslinking of BCRs on human EU12μHC+immature B cells resulted in complete internalization of cell surface BCRs. After loss of cell surface BCRs, restimulation of EU12μHC+cells showed impaired Ca2+flux, delayed SYK phosphorylation, and decreased CD19 and FOXO1 phosphorylation, which differ from those in mature Daudi or Ramos B cells with partial internalization of BCRs. In contrast, sustained phosphorylation and reactivation of ERK upon restimulation were observed in the EU12μHC+cells after BCR internalization. Taken together, these results show that complete internalization of cell surface BCRs in EU12μHC+cells specifically alters the downstream signaling events, which may favor receptor editing versus cell activation.