Notch2 signaling governs activated B cells to form memory B cells
Tingting Xu,
Tianyu Zhang,
Chuqiao Xu,
Fang Yang,
Wenqian Zhang,
Chuanxin Huang
Affiliations
Tingting Xu
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 the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Biliary Tract Disease Research, Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Tianyu Zhang
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 the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Chuqiao Xu
Departments of Dermatology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Fang Yang
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 the Chinese Ministry of Education, 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; Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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 the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Biliary Tract Disease Research, Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Corresponding author
Summary: Memory B cells (MBCs) are essential for humoral immunological memory and can emerge during both the pre-germinal center (GC) and GC phases. However, the transcription regulators governing MBC development remain poorly understood. Here, we report that the transcription regulator Notch2 is highly expressed in MBCs and their precursors at the pre-GC stage and required for MBC development without influencing the fate of GC and plasma cells. Mechanistically, Notch2 signaling promotes the expression of complement receptor CD21 and augments B cell receptor (BCR) signaling. Reciprocally, BCR activation up-regulates Notch2 surface expression in activated B cells via a translation-dependent mechanism. Intriguingly, Notch2 is dispensable for GC-derived MBC formation. In summary, our findings establish Notch2 as a pivotal transcription regulator orchestrating MBC development through the reciprocal enforcement of BCR signaling during the pre-GC phase and suggest that the generation of GC-independent and -dependent MBCs is governed by distinct transcriptional mechanisms.
