@article{063d1ccdb9184aba918492b766e1df01,
title = "Transcription factor Ascl2 promotes germinal center B cell responses by directly regulating AID transcription",
abstract = "During germinal center (GC) reactions, activated B cells undergo clonal expansion and functional maturation to produce high-affinity antibodies and differentiate into plasma and memory cells, accompanied with class-switching recombination (CSR) and somatic hypermutation (SHM). Activation-induced cytidine deaminase (AID) is responsible for both CSR and SHM in GC B cells. Transcriptional mechanisms underlying AID regulation and GC B cell reactions are still not well understood. Here, we show that expression of Ascl2 transcription factor is upregulated in GC B cells. Ectopic expression of Ascl2 promotes GC B cell development and enhances antibody production and affinity maturation. Conversely, deletion of Ascl2 in B cells impairs the GC response. Genome-wide analysis reveals that Ascl2 directly regulates GC B cell-related genes, including AID; ectopic expression of AID in Ascl2-deficient B cells rescues their antibody defects. Thus, Ascl2 regulates AID transcription and promotes GC B cell responses.",
author = "Lin Sun and Xiaohong Zhao and Xindong Liu and Bo Zhong and Hong Tang and Wei Jin and Hans Clevers and Hui Wang and Xiaohu Wang and Chen Dong",
note = "Funding Information: This work was supported by grants from National Key Research and Development Program of China ( 2016YFC0906200 to C.D.), National Natural Science Foundation of China ( 31630022 , 31821003 , and 31991170 to C.D.), and Beijing Municipal Science and Technology ( Z181100001318007 to C.D.). We also thank the flow cytometry core facility (Institute for Immunology), the animal platform at Tsinghua University, and members of the Dong laboratory for technical support and assistance. Funding Information: This work was supported by grants from National Key Research and Development Program of China (2016YFC0906200 to C.D.), National Natural Science Foundation of China (31630022, 31821003, and 31991170 to C.D.), and Beijing Municipal Science and Technology (Z181100001318007 to C.D.). We also thank the flow cytometry core facility (Institute for Immunology), the animal platform at Tsinghua University, and members of the Dong laboratory for technical support and assistance. L.S. designed and performed the experiments and wrote the manuscript. B.Z. X.L. and H.W. generated the Ascl2 ZsGreen mice. X.Z. contributed to the data analysis of RNA-seq and ChIP-seq. W.J. contributed to design and performed the experiments. X.W. reviewed and edited the manuscript. C.D. designed the research and edited the manuscript. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2021",
month = jun,
day = "1",
doi = "10.1016/j.celrep.2021.109188",
language = "English",
volume = "35",
pages = "1--12",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "9",
}