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Notch2-mediated plasticity between marginal zone and follicular B cells
Markus Lechner1, Thomas Engleitner2,3,4, Tea Babushku1
1Research Unit Gene Vectors, Helmholtz Zentrum München GmbH, German Research Center for Environmental Health, München, Germany.
Nature Communications
|February 18, 2021
Summary
Mature Follicular B (FoB) cells can transform into Marginal Zone B (MZB) cells. This plasticity is triggered by Notch2 signaling, revealing a dynamic relationship between these key B cell populations.
Area of Science:
- Immunology
- Cell Biology
- Developmental Biology
Background:
- Follicular B (FoB) and marginal zone B (MZB) cells are distinct splenic B cell subsets.
- Their differentiation is Notch2-dependent, originating from transitional B cells.
- Fibroblast-derived DLL-1 provides Notch2 signals in B cell follicles.
Purpose of the Study:
- To investigate if mature FoB cells can differentiate into MZB cells upon receiving a Notch2 signal.
- To explore the plasticity between FoB and MZB cell lineages.
Main Methods:
- Induced expression of Notch2 intracellular domain (Notch2IC) in FoB cells.
- Analysis of cell surface phenotype, localization, immunological function, and transcriptome.
- In vivo studies in immunocompetent wildtype mice.
Main Results:
- Induced Notch2IC expression in FoB cells successfully reprogrammed them into MZB cells.
- These reprogrammed cells exhibited MZB cell characteristics in phenotype, location, function, and gene expression.
- Lineage conversion was observed in living, immunocompetent mice.
Conclusions:
- Mature FoB and MZB cells exhibit plasticity, interconverting between lineages.
- Activation of Notch2 signaling is a key driver for this FoB to MZB cell lineage conversion.
- This highlights a novel mechanism of B cell subset regulation in vivo.
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