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,
Hua-bing Li,
Chiqi Chen,
Junke Zheng,
Zhen Zhang,
Fubin Li,
Nan Shen,
Wenqian Zhang,
Ari Melnick,
Chuanxin Huang
Affiliations
Qianwen Hu
Center for Immune-Related Diseases at Shanghai Institute of Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Tingting Xu
Center for Immune-Related Diseases at Shanghai Institute of Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Min Zhang
Shanghai Pediatric Congenital Heart Disease Institute and Pediatric Translational Medicine Institute, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Heng Zhang
Center for Immune-Related Diseases at Shanghai Institute of Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Yongbo Liu
Center for Immune-Related Diseases at Shanghai Institute of Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Hua-bing Li
Center for Immune-Related Diseases at Shanghai Institute of Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Chiqi Chen
Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Junke Zheng
Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Zhen Zhang
Shanghai Pediatric Congenital Heart Disease Institute and Pediatric Translational Medicine Institute, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Fubin Li
Center for Immune-Related Diseases at Shanghai Institute of Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Nan Shen
Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Wenqian Zhang
Center for Immune-Related Diseases at Shanghai Institute of Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Corresponding author
Ari Melnick
Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medicine, Cornell University, Ithaca, NY, USA; Corresponding author
Chuanxin Huang
Center for Immune-Related Diseases at Shanghai Institute of Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Corresponding author
Summary: 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.
