Journal
CELL REPORTS
Volume 40, Issue 1, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2022.111035
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Funding
- National Key R&D Program of China [2021YFA1301403, 2019YFA0111000]
- National Natural Science Foundation of China [31870872, 32070881, 32000618]
- Shanghai Science and Technology Committee [20ZR1448800, 20JC1410100]
- Innovative Research Team of High-level Local Universities in Shanghai [ZDCX20211800]
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The study reveals that Bach2 protein and transcripts in activated B cells have differential roles in controlling their cell-fate outcomes and the fate of their descendant effector cells.
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 gov-erning these processes remain to be elucidated. Here, we show that transcription factor Bach2 protein in acti-vated 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 pro-moting 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 concen-trations 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.
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