Accelerated plasma-cell differentiation in Bach2-deficient mouse B cells is caused by altered IRF4 functions

ABSTRACT: Transcription factors BACH2 and IRF4 are both essential for antibody class-switch recombination (CSR) in activated B lymphocytes, while they oppositely regulate differentiation of plasma cells (PC). Here, we investigated how BACH2 and IRF4interact during CSR and plasma-cell differentiation. We found that BACH2 organizes heterochromatin formation of target gene loci in mouse splenic B cells, including targets of IRF4 activation such as Aicda, an inducer of CSR, and Prdm1, a master plasma-cell regulator. Release of these gene loci from heterochromatin in response to B-cell receptor stimulation was coupled to AKT-mTOR pathway activation. In Bach2-deficient B cells, PC genes' activation depended on IRF4 protein accumulation, without an increase in Irf4 mRNA. Mechanistically, a PU.1-IRF4 hetero

SUBMITTER: Dr. Kyoko Ochiai 

PROVIDER: S-SCDT-10_1038-S44318-024-00077-6 | biostudies-other |

REPOSITORIES: biostudies-other