Diverging regulation of Bach2 protein and RNA expression determine cell fate in early B cell response
Qianwen Hu, Tingting Xu, Min Zhang, Heng Zhang, Yongbo Liu, Huabing Li, Chiqi Chen, Junke Zheng, Zhen Zhang, Fubin Li, Nan Shen, Wenqian Zhang, Ari Melnick, Chuanxin Huang
Abstract
During the early phase of primary humoral responses, activated B cells can differentiate into different types of effector cells, dependent on B cell receptor affinity for antigen. However, the pivotal transcription factors governing these processes remain to be elucidated. Here, we show that transcription factor Bach2 protein in activated B cells is transiently induced by affinity-related signals and mechanistic target of rapamycin complex 1 (mTORC1)-dependent translation to restrain their expansion and differentiation into plasma cells while promoting memory and germinal center (GC) B cell fates. Affinity-related signals also downregulate Bach2 mRNA expression in activated B cells and their descendant memory B cells. Sustained and higher concentrations of Bach2 antagonize the GC fate. Repression of Bach2 in memory B cells predisposes their cell-fate choices upon memory recall. Our study reveals that differential dynamics of Bach2 protein and transcripts in activated B cells control their cell-fate outcomes and imprint the fates of their descendant effector cells.