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

Lin Sun, Xiaohong Zhao, Xindong Liu, Bo Zhong, Hong Tang, Wei Jin, Hans Clevers, Hui Wang, Xiaohu Wang, Chen Dong

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgaveArtikelWetenschappelijkpeer review


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.

Originele taal-2Engels
Pagina's (van-tot)109188
TijdschriftCell Reports
Nummer van het tijdschrift9
StatusGepubliceerd - 01 jun. 2021


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