生发中心
亲和力成熟
体细胞突变
B细胞
细胞生物学
细胞周期
化学
细胞
有丝分裂
生物
亲和层析
分子生物学
主轴装置
抗原
细胞分裂
生物化学
抗体
遗传学
酶
作者
Jingjing Chen,Zhenming Cai,Le Zhang,Yuye Yin,Xufeng Chen,Chao Chen,Yang Zhang,Sulan Zhai,Xuehui Long,Xiaolong Liu,Xiaoming Wang
出处
期刊:Journal of Immunology
[The American Association of Immunologists]
日期:2017-04-27
卷期号:198 (11): 4304-4311
被引量:9
标识
DOI:10.4049/jimmunol.1700159
摘要
Abstract 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.
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