Center for Innovation in Immunoregulative Technology and Therapeutics, Graduate School of Medicine, Kyoto University, Yoshidakonoecho, Sakyoku, Kyoto 606-8501, Japan.
Center for Innovation in Immunoregulative Technology and Therapeutics, Graduate School of Medicine, Kyoto University, Yoshidakonoecho, Sakyoku, Kyoto 606-8501, Japan.
Biochem Biophys Res Commun. 2014 Mar 14;445(3):572-7. doi: 10.1016/j.bbrc.2014.02.037. Epub 2014 Feb 15.
It has been shown that cytoplasmic tail of the IgG1 B cell receptors (BCRs) are essential for the induction of T-dependent immune responses. Also it has been revealed that unique tyrosine residue in the cytoplasmic tail of IgG2a has the potential of being phosphorylated at tyrosine and that this phosphorylation modulates BCR signaling. However, it still remains unclear whether such phosphorylation of IgG cytoplasmic tail is involved in the regulation of BCR surface expression. In order to approach the issue, we established and analyzed the cell lines which express wild-type or mutated forms of IgG1 BCR. As the result, we found that IgG1 BCR expressed normally on the surface of A20 B cell line independent of the cytoplasmic tail. In contrast, IgG1 BCR whose cytoplasmic tyrosine was replaced with glutamic acid which mimics phosphorylated tyrosine, was expressed most efficiently on the surface of non-B lineage cells and Igβ-down-regulated B cell lines. These results suggest that tyrosine residue in IgG cytoplasmic tail is playing a essential role for the efficient expression of IgG BCR on the cell surface when BCR associated signaling molecules, including Igβ, are down-regulated.
已经表明，IgG1 B 细胞受体 (BCR) 的细胞质尾部对于诱导 T 依赖性免疫应答是必不可少的。此外，还揭示了 IgG2a 细胞质尾部中的独特酪氨酸残基具有在酪氨酸上被磷酸化的潜力，并且这种磷酸化调节 BCR 信号转导。然而，仍然不清楚 IgG 细胞质尾部的这种磷酸化是否参与 BCR 表面表达的调节。为了解决这个问题，我们建立并分析了表达野生型或突变型 IgG1 BCR 的细胞系。结果发现，A20 B 细胞系表面正常表达 IgG1 BCR，而不依赖于细胞质尾部。相比之下，将细胞质中的酪氨酸替换为模拟磷酸化酪氨酸的谷氨酸的 IgG1 BCR，在非 B 谱系细胞和 Igβ 下调的 B 细胞系上表达效率最高。这些结果表明，当与 BCR 相关的信号分子（包括 Igβ）下调时，IgG 细胞质尾部中的酪氨酸残基对于 IgG BCR 在细胞表面的有效表达起着至关重要的作用。
