Differential organization of tonic and chronic B cell antigen receptors in the plasma membrane

Differential organization of tonic and chronic B cell antigen receptors in the plasma membrane
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DOI:
10.1038/s41467-019-08677-1
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发表时间:
2019-02-18
影响因子:
16.6
通讯作者:
Opazo, Felipe
Opazo, Felipe
中科院分区:
综合性期刊1区
文献类型:
--
作者:
de Castro, Maria Angela Gomes;Wildhagen, Hanna;Opazo, Felipe

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刺激B细胞抗原受体(BCR)触发信号通路,促进B细胞向浆细胞分化。尽管BCR在B细胞活化中起着关键作用,但BCR在静息和抗原激活的B细胞表面的组织结构尚不清楚。在这里,我们使用STED超分辨率显微镜显示,含有IgM的BCR主要以单体和二聚体的形式存在于静息B细胞的质膜中,但在刺激下形成更高的寡聚体。相比之下,慢性淋巴细胞白血病来源的BCR在没有刺激的情况下形成二聚体和寡聚体,但在没有刺激的B细胞中,单一的氨基酸交换将其组织恢复为单体。因此,我们用于定量分析细胞表面蛋白的超分辨率显微镜方法可能有助于揭示各种细胞类型中免疫受体的纳米级组织。
Stimulation of the B cell antigen receptor (BCR) triggers signaling pathways that promote the differentiation of B cells into plasma cells. Despite the pivotal function of BCR in B cell activation, the organization of the BCR on the surface of resting and antigen-activated B cells remains unclear. Here we show, using STED super-resolution microscopy, that IgM-containing BCRs exist predominantly as monomers and dimers in the plasma membrane of resting B cells, but form higher oligomeric clusters upon stimulation. By contrast, a chronic lymphocytic leukemia-derived BCR forms dimers and oligomers in the absence of a stimulus, but a single amino acid exchange reverts its organization to monomers in unstimulated B cells. Our super-resolution microscopy approach for quantitatively analyzing cell surface proteins may thus help reveal the nanoscale organization of immunoreceptors in various cell types.