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

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 classswitching 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.

Automated summary

The transcription factor Ascl2 is upregulated in GC B cells and promotes their development, antibody production, and affinity maturation. Deletion of Ascl2 impairs GC response, but ectopic expression of AID in Ascl2-deficient B cells can rescue antibody defects. Thus, Ascl2 regulates AID transcription and enhances GC B cell responses.