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Notch2 controls developmental fate choices between germinal center and marginal zone B cells upon immunization

Author

Listed:
  • Tea Babushku

    (German Research Center for Environmental Health
    Technical University of Munich)

  • Markus Lechner

    (German Research Center for Environmental Health)

  • Stefanie Ehrenberg

    (German Research Center for Environmental Health)

  • Ursula Rambold

    (German Research Center for Environmental Health)

  • Marc Schmidt-Supprian

    (Technical University of Munich)

  • Andrew J. Yates

    (Columbia University Irving Medical Center)

  • Sanket Rane

    (Columbia University)

  • Ursula Zimber-Strobl

    (German Research Center for Environmental Health
    Member of the German Center for Lung Research (DZL))

  • Lothar J. Strobl

    (German Research Center for Environmental Health
    Member of the German Center for Lung Research (DZL))

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.

Suggested Citation

  • Tea Babushku & Markus Lechner & Stefanie Ehrenberg & Ursula Rambold & Marc Schmidt-Supprian & Andrew J. Yates & Sanket Rane & Ursula Zimber-Strobl & Lothar J. Strobl, 2024. "Notch2 controls developmental fate choices between germinal center and marginal zone B cells upon immunization," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46024-1
    DOI: 10.1038/s41467-024-46024-1
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    References listed on IDEAS

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    1. Markus Lechner & Thomas Engleitner & Tea Babushku & Marc Schmidt-Supprian & Roland Rad & Lothar J. Strobl & Ursula Zimber-Strobl, 2021. "Notch2-mediated plasticity between marginal zone and follicular B cells," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    2. Tal I. Arnon & Robert M. Horton & Irina L. Grigorova & Jason G. Cyster, 2013. "Visualization of splenic marginal zone B-cell shuttling and follicular B-cell egress," Nature, Nature, vol. 493(7434), pages 684-688, January.
    3. Wing Fuk Chan & Hannah D. Coughlan & Jie H. S. Zhou & Christine R. Keenan & Naiara G. Bediaga & Philip D. Hodgkin & Gordon K. Smyth & Timothy M. Johanson & Rhys S. Allan, 2021. "Pre-mitotic genome re-organisation bookends the B cell differentiation process," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
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