Notch2 controls developmental fate choices between germinal center and marginal zone B cells upon immunization
Abstract Sustained Notch2 signals induce trans-differentiation of Follicular B (FoB) cells into Marginal Zone B (MZB) cells in mice, but the physiology underlying this differentiation pathway is still elusive. Here, we demonstrate that most B cells receive a basal Notch signal, which is intensified...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-03-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-46024-1 |
| _version_ | 1797274097225302016 |
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| author | Tea Babushku Markus Lechner Stefanie Ehrenberg Ursula Rambold Marc Schmidt-Supprian Andrew J. Yates Sanket Rane Ursula Zimber-Strobl Lothar J. Strobl |
| author_facet | Tea Babushku Markus Lechner Stefanie Ehrenberg Ursula Rambold Marc Schmidt-Supprian Andrew J. Yates Sanket Rane Ursula Zimber-Strobl Lothar J. Strobl |
| author_sort | Tea Babushku |
| collection | DOAJ |
| description | Abstract Sustained Notch2 signals induce trans-differentiation of Follicular B (FoB) cells into Marginal Zone B (MZB) cells in mice, but the physiology underlying this differentiation pathway is still elusive. Here, we demonstrate that most B cells receive a basal Notch signal, which is intensified in pre-MZB and MZB cells. Ablation or constitutive activation of Notch2 upon T-cell-dependent immunization reveals an interplay between antigen-induced activation and Notch2 signaling, in which FoB cells that turn off Notch2 signaling enter germinal centers (GC), while high Notch2 signaling leads to generation of MZB cells or to initiation of plasmablast differentiation. Notch2 signaling is dispensable for GC dynamics but appears to be re-induced in some centrocytes to govern expansion of IgG1+ GCB cells. Mathematical modelling suggests that antigen-activated FoB cells make a Notch2 dependent binary fate-decision to differentiate into either GCB or MZB cells. This bifurcation might serve as a mechanism to archive antigen-specific clones into functionally and spatially diverse B cell states to generate robust antibody and memory responses. |
| first_indexed | 2024-03-07T14:53:30Z |
| format | Article |
| id | doaj.art-6e11745d8d724719a32b1e692199e761 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-07T14:53:30Z |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-6e11745d8d724719a32b1e692199e7612024-03-05T19:32:46ZengNature PortfolioNature Communications2041-17232024-03-0115112010.1038/s41467-024-46024-1Notch2 controls developmental fate choices between germinal center and marginal zone B cells upon immunizationTea Babushku0Markus Lechner1Stefanie Ehrenberg2Ursula Rambold3Marc Schmidt-Supprian4Andrew J. Yates5Sanket Rane6Ursula Zimber-Strobl7Lothar J. Strobl8Research Unit Gene Vectors, Research Group B Cell Development and Activation, Helmholtz Zentrum München, German Research Center for Environmental HealthResearch Unit Gene Vectors, Research Group B Cell Development and Activation, Helmholtz Zentrum München, German Research Center for Environmental HealthResearch Unit Gene Vectors, Research Group B Cell Development and Activation, Helmholtz Zentrum München, German Research Center for Environmental HealthInstitute of Asthma and Allergy Prevention, Helmholtz Zentrum München, German Research Center for Environmental HealthTranslaTUM, Center for Translational Cancer Research, Technical University of MunichDepartment of Pathology and Cell Biology, Columbia University Irving Medical CenterIrving Institute for Cancer Dynamics, Columbia UniversityResearch Unit Gene Vectors, Research Group B Cell Development and Activation, Helmholtz Zentrum München, German Research Center for Environmental HealthResearch Unit Gene Vectors, Research Group B Cell Development and Activation, Helmholtz Zentrum München, German Research Center for Environmental HealthAbstract Sustained Notch2 signals induce trans-differentiation of Follicular B (FoB) cells into Marginal Zone B (MZB) cells in mice, but the physiology underlying this differentiation pathway is still elusive. Here, we demonstrate that most B cells receive a basal Notch signal, which is intensified in pre-MZB and MZB cells. Ablation or constitutive activation of Notch2 upon T-cell-dependent immunization reveals an interplay between antigen-induced activation and Notch2 signaling, in which FoB cells that turn off Notch2 signaling enter germinal centers (GC), while high Notch2 signaling leads to generation of MZB cells or to initiation of plasmablast differentiation. Notch2 signaling is dispensable for GC dynamics but appears to be re-induced in some centrocytes to govern expansion of IgG1+ GCB cells. Mathematical modelling suggests that antigen-activated FoB cells make a Notch2 dependent binary fate-decision to differentiate into either GCB or MZB cells. This bifurcation might serve as a mechanism to archive antigen-specific clones into functionally and spatially diverse B cell states to generate robust antibody and memory responses.https://doi.org/10.1038/s41467-024-46024-1 |
| spellingShingle | Tea Babushku Markus Lechner Stefanie Ehrenberg Ursula Rambold Marc Schmidt-Supprian Andrew J. Yates Sanket Rane Ursula Zimber-Strobl Lothar J. Strobl Notch2 controls developmental fate choices between germinal center and marginal zone B cells upon immunization Nature Communications |
| title | Notch2 controls developmental fate choices between germinal center and marginal zone B cells upon immunization |
| title_full | Notch2 controls developmental fate choices between germinal center and marginal zone B cells upon immunization |
| title_fullStr | Notch2 controls developmental fate choices between germinal center and marginal zone B cells upon immunization |
| title_full_unstemmed | Notch2 controls developmental fate choices between germinal center and marginal zone B cells upon immunization |
| title_short | Notch2 controls developmental fate choices between germinal center and marginal zone B cells upon immunization |
| title_sort | notch2 controls developmental fate choices between germinal center and marginal zone b cells upon immunization |
| url | https://doi.org/10.1038/s41467-024-46024-1 |
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