Lis1 Regulates Germinal Center B Cell Antigen Acquisition and Affinity Maturation.

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. Copyright © 2017 by The American Association of Immunologists, Inc.

Citation

Jingjing Chen, Zhenming Cai, Le Zhang, Yuye Yin, Xufeng Chen, Chao Chen, Yang Zhang, Sulan Zhai, Xuehui Long, Xiaolong Liu, Xiaoming Wang. Lis1 Regulates Germinal Center B Cell Antigen Acquisition and Affinity Maturation. Journal of immunology (Baltimore, Md. : 1950). 2017 Jun 01;198(11):4304-4311

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PMID: 28446568

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