Lis1 Regulates Germinal Center B Cell Antigen Acquisition and Affinity Maturation
Lis1 Regulates Germinal Center B Cell Antigen Acquisition and Affinity Maturation
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Lis1 调节生发中心 B 细胞抗原的获取和亲和力成熟。
DOI：
10.4049/jimmunol.1700159
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发表时间：
2017-06-01
影响因子：
4.4
通讯作者：
Wang, Xiaoming
中科院分区：
文献类型：
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作者：
Chen, Jingjing;Cai, Zhenming;Wang, Xiaoming
生发中心（GC）是激活的B细胞经历快速扩增、体细胞超突变和亲和成熟的部位。亲和成熟是一个由年龄驱动的选择过程。GC B细胞获得和显示Ag的数量决定了其是否能被正选择，因此必须严格调节Ag的获得以确保有效的亲和成熟。细胞扩增提供了足够数量的GC B细胞和抗体，而亲和成熟提高了抗体的质量。在本研究中，我们发现Lis1是GC B细胞Ag获取能力的细胞内在调节剂。缺乏Lis1导致聚合肌动蛋白的重新分布和f -肌动蛋白在尾足的积累；GC B细胞获得并显示了更多的Ags，这可能降低了选择的严格性。因此，lis1缺陷小鼠的亲和成熟受到损害。与此一致的是，Lis1在GC B细胞中的过表达导致Ag的获取和显示减少。此外，GC B细胞扩增需要Lis1， Lis1缺乏阻断了有丝分裂期的细胞周期，GC B细胞容易凋亡。综上所述，我们认为Lis1是GC B细胞扩增、亲和成熟和维持功能完整的GC应答所必需的，从而保证了Ab应答的数量和质量。
The germinal center (GC) is the site where activated B cells undergo rapid expansions, somatic hypermutation, and affinity maturation. Affinity maturation is a process of Ag-driven selection. The amount of Ag acquired and displayed by GC B cells determines whether it can be positively selected, and therefore Ag acquisition has to be tightly regulated to ensure the efficient affinity maturation. Cell expansion provides sufficient quantity of GC B cells and Abs, whereas affinity maturation improves the quality of Abs. In this study, we found that Lis1 is a cell-intrinsic regulator of Ag acquisition capability of GC B cells. Lack of Lis1 resulted in redistribution of polymerized actin and accumulation of F-actin at uropod; larger amounts of Ags were acquired and displayed by GC B cells, which presumably reduced the selection stringency. Affinity maturation was thus compromised in Lis1-deficient mice. Consistently, overexpression of Lis1 in GC B cells led to less Ag acquisition and display. Additionally, Lis1 is required for GC B cell expansion, and Lis1 deficiency blocked the cell cycle at the mitotic phase and GC B cells were prone to apoptosis. Overall, we suggest that Lis1 is required for GC B cell expansion, affinity maturation, and maintaining functional intact GC response, thus ensuring both the quantity and quality of Ab response.