Coupling between B cell receptor and phospholipase C-γ2 is essential for mature B cell development

Coupling between B cell receptor and phospholipase C-γ2 is essential for mature B cell development
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DOI:
10.1084/jem.20030280
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发表时间:
2003-08-18
影响因子:
15.3
通讯作者:
Kurosaki, T
Kurosaki, T
中科院分区:
医学1区
文献类型:
--
作者:
Hikida, M;Johmura, S;Kurosaki, T

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BAFF 受体 (BAFF-R) 和 B 细胞受体 (BCR) 是已知对于从小型 B 细胞向成熟 B 细胞进展至关重要的两条信号传导途径。在这里,我们首先证明 BAFF-R 介导的生存信号需要磷脂酶 C (PLC)-gamma2。然后,我们研究了 PLC-gamma2(-/-) 小鼠中成熟 B 细胞数量减少是否是由 BCP 或 BAFF-R 信号传导缺陷引起的问题。我们发现,抑制 BCR 和 PLC-gamma2 之间偶联的 PLC-gamma2 SH2 突变体尽管支持 BAFF 依赖性存活,但无法恢复 B 细胞成熟。因此,我们的数据表明,PLC-gamma2 提供的 BAFF-R 介导的生存信号不足以促进 B 细胞成熟,此外,B 细胞发育需要 BCR 激活 PLC-gamma2。
Two signaling pathways known to be essential for progression from miniature to mature B cells are BAFF receptor (BAFF-R) and the B cell receptor (BCR). Here, we first show that phospholipase C (PLC)-gamma2 is required for a BAFF-R-mediated survival signal. Then, we have examined the question of whether the reduced number of mature B cells in PLC-gamma2(-/-) mice is caused by a defect in either BCP, or BAFF-R signaling. We find that a PLC-gamma2 SH2 mutant, which inhibits coupling between BCR and PLC-gamma2, fails to restore B cell maturation, despite supporting BAFF-dependent survival. Therefore, our data suggest that the BAFF-R-mediated survival signal, provided by PLC-gamma2, is not sufficient to promote B cell maturation, and that, in addition, activation of PLC-gamma2 by BCR is required for B cell development.