Transcription factor Ascl2 promotes germinal center B cell responses by directly regulating AID transcription

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 - Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

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.

U2 - 10.1016/j.celrep.2021.109188

DO - 10.1016/j.celrep.2021.109188

M3 - Article

C2 - 34077723

SN - 2211-1247

VL - 35

SP - 109188

JO - Cell Reports

JF - Cell Reports

IS - 9

ER -