FcμR Interacts and Cooperates with the B Cell Receptor To Promote B Cell Survival
FcμR Interacts and Cooperates with the B Cell Receptor To Promote B Cell Survival
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FcμR 与 B 细胞受体相互作用并协同促进 B 细胞存活
DOI：
10.4049/jimmunol.1402352
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发表时间：
2015-04-01
影响因子：
4.4
通讯作者：
Wang, Ji-Yang
中科院分区：
文献类型：
--
作者：
Ouchida, Rika;Lu, Qing;Wang, Ji-Yang
IgM FcR（Fc μ R）促进B细胞存活，但其分子机制仍不清楚。我们使用Fc μ R-/-和野生型小鼠表明，Fc μ R特异性增强了由BCR与F（ab '）（2）-抗IgM抗体交联诱导的B细胞存活，而当B细胞被CD 40连接或LPS刺激激活时，对存活没有影响。抗IgM刺激可显著上调Fc mu R表达，这可能促进这些细胞中Fc mu R信号传导增强。免疫荧光和共聚焦显微镜分析表明，Fc μ R与原代B细胞质膜上的BCR共定位。免疫共沉淀分析进一步揭示了Fc μ R与BCR复合物的物理相互作用。由于NF-κ B在B细胞存活中起重要作用，我们分析了Fc μ R是否参与BCR触发的NF-κ B活化。Fc μ R不影响经典NF-κ B活化途径特征性的BCR触发的I κ B α磷酸化，但促进非经典NF-κ B途径组分p52的产生。与升高的p52水平一致，Fc mu R增强了BCR触发的抗凋亡蛋白BCL-xL的表达。重要的是，在不存在BCR信号传导的情况下，单独的Fc μ R刺激对IkBa磷酸化或p52和BCL-xL的表达没有影响。因此，Fc mu R依赖于BCR信号来激活非经典NF-κ B通路并增强B细胞存活。这些结果揭示了Fc mu R和BCR信号传导的下游串扰，并提供了对BCR刺激后Fc mu R介导的B细胞存活增强的机制性见解。
The IgM FcR (Fc mu R) promotes B cell survival, but the molecular mechanism remains largely unknown. We show using Fc mu R-/- and wild-type mice that Fc mu R specifically enhanced B cell survival induced by BCR cross-linking with F(ab ')(2)-anti-IgM Abs while having no effect on survival when the B cells were activated by CD40 ligation or LPS stimulation. Fc mu R expression was markedly upregulated by anti-IgM stimulation, which may promote enhanced Fc mu R signaling in these cells. Immunofluorescence and confocal microscopy analyses demonstrated that Fc mu R colocalized with the BCR on the plasma membrane of primary B cells. Coimmunoprecipitation analysis further revealed that Fc mu R physically interacted with the BCR complex. Because NF-kappa B plays a prominent role in B cell survival, we analyzed whether Fc mu R was involved in BCR-triggered NF-kappa B activation. Fc mu R did not affect BCR-triggered I kappa B alpha phosphorylation characteristic of the canonical NF-kappa B activation pathway but promoted the production of the noncanonical NF-kappa B pathway component p52. Consistent with the elevated p52 levels, Fc mu R enhanced BCR-triggered expression of the antiapoptotic protein BCL-xL. Importantly, Fc mu R stimulation alone in the absence of BCR signaling had no effect on either IkBa phosphorylation or the expression of p52 and BCL-xL. Therefore, Fc mu R relied on the BCR signal to activate the noncanonical NF-kappa B pathway and enhance B cell survival. These results reveal a cross-talk downstream of Fc mu R and BCR signaling and provide mechanistic insight into Fc mu R-mediated enhancement of B cell survival after BCR stimulation.