1. Notch2 signaling governs activated B cells to form memory B cells.
- Author
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Xu T, Zhang T, Xu C, Yang F, Zhang W, and Huang C
- Subjects
- Animals, Mice, Mice, Inbred C57BL, Germinal Center immunology, Germinal Center metabolism, B-Lymphocytes metabolism, B-Lymphocytes immunology, Immunologic Memory, Receptors, Complement 3d metabolism, Signal Transduction, Receptor, Notch2 metabolism, Receptor, Notch2 genetics, Receptors, Antigen, B-Cell metabolism, Memory B Cells metabolism, Memory B Cells immunology, Lymphocyte Activation immunology
- Abstract
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., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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