TY - JOUR
T1 - Transcription factor Ascl2 promotes germinal center B cell responses by directly regulating AID transcription
AU - Sun, Lin
AU - Zhao, Xiaohong
AU - Liu, Xindong
AU - Zhong, Bo
AU - Tang, Hong
AU - Jin, Wei
AU - Clevers, Hans
AU - Wang, Hui
AU - Wang, Xiaohu
AU - Dong, Chen
N1 - 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:
© 2021 The Authors
PY - 2021/6/1
Y1 - 2021/6/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85107043225
U2 - 10.1016/j.celrep.2021.109188
DO - 10.1016/j.celrep.2021.109188
M3 - Article
C2 - 34077723
AN - SCOPUS:85107043225
SN - 2211-1247
VL - 35
SP - 1
EP - 12
JO - Cell Reports
JF - Cell Reports
IS - 9
M1 - 109188
ER -