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Babushku, T. ; Lechner, M. ; Ehrenberg, S. ; Rambold, U. ; Schmidt-Supprian, M.* ; Yates, A.J.* ; Rane, S.* ; Zimber-Strobl, U. ; Strobl, L.J.

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

Nat. Commun. 15:1960 (2024)

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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.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Positive Selection; Gene-expression; Distinct; Blimp-1; Differentiation; Visualization; Delta-like-1; Activation; Ligands; Bcl6

ISSN (print) / ISBN 2041-1723

e-ISSN 2041-1723

Journal Nature Communications

Quellenangaben Volume: 15, Issue: 1, Article Number: 1960

Publisher Nature Publishing Group

Publishing Place London

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Research Unit Gene Vector (AGV)
Institute of Asthma and Allergy Prevention (IAP)
Lung Health and Immunity (LHI)

Grants Deutsche Forschungsgemeinschaft (German Research Foundation)
National Institute of Allergy and Infectious Diseases of the National Institutes of Health