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CX3CR1 positively regulates BCR signaling coupled with cell metabolism via negatively controlling actin remodeling.
Cellular and Molecular Life Sciences ( IF 6.2 ) Pub Date : 2020-02-04 , DOI: 10.1007/s00018-019-03416-7
Na Li 1 , Panpan Jiang 2 , Anwei Chen 3 , Xi Luo 4 , Yukai Jing 2 , Lu Yang 2 , Danqing Kang 2 , Qiuyue Chen 1 , Ju Liu 2 , Jiang Chang 2 , Julia Jellusova 5 , Heather Miller 6 , Lisa Westerberg 7 , Cong-Yi Wang 4 , Quan Gong 1 , Chaohong Liu 2
Affiliation  

As an important chemokine receptor, the role of CX3CR1 has been studied extensively on the migration of lymphocytes including T and B cells. Although CX3CR1+ B cells have immune suppressor properties, little is known about its role on the regulation of BCR signaling and B cell differentiation as well as the underlying molecular mechanism. We have used CX3CR1 KO mice to study the effect of CX3CR1 deficiency on BCR signaling and B cell differentiation. Interestingly, we found that proximal BCR signaling, such as the activation of CD19, BTK and SHIP was reduced in CX3CR1 KO B cells upon antigenic stimulation. However, the activation of mTORC signaling was enhanced. Mechanistically, we found that the reduced BCR signaling in CX3CR1 KO B cells was due to reduced BCR clustering, which is caused by the enhanced actin accumulation by the plasma membrane via increased activation of WASP. This caused an increased differentiation of MZ B cells in CX3CR1 KO mice and an enhanced generation of plasma cells (PC) and antibodies. Our study shows that CX3CR1 regulates BCR signaling via actin remodeling and affects B cell differentiation and the humoral immune response.



中文翻译:


CX3CR1 通过负向控制肌动蛋白重塑,正向调节与细胞代谢相关的 BCR 信号传导。



作为一种重要的趋化因子受体,CX3CR1在包括T细胞和B细胞在内的淋巴细胞迁移中的作用已被广泛研究。尽管CX3CR1 + B细胞具有免疫抑制特性,但对其在BCR信号传导和B细胞分化调节中的作用以及潜在的分子机制知之甚少。我们使用 CX3CR1 KO 小鼠来研究 CX3CR1 缺陷对 BCR 信号传导和 B 细胞分化的影响。有趣的是,我们发现近端 BCR 信号传导,例如 CD19、BTK 和 SHIP 的激活,在抗原刺激后在 CX3CR1 KO B 细胞中减少。然而,mTORC 信号传导的激活增强。从机制上讲,我们发现 CX3CR1 KO B 细胞中 BCR 信号传导减少是由于 BCR 聚类减少所致,而 BCR 聚类减少是由于 WASP 激活增加导致质膜肌动蛋白积累增强所致。这导致 CX3CR1 KO 小鼠中 MZ B 细胞的分化增加,并增加浆细胞 (PC) 和抗体的生成。我们的研究表明,CX3CR1 通过肌动蛋白重塑调节 BCR 信号传导,并影响 B 细胞分化和体液免疫反应。

更新日期:2020-02-04
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