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

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
04 Mar 2024
Historique:
received: 08 11 2022
accepted: 12 02 2024
medline: 5 3 2024
pubmed: 5 3 2024
entrez: 4 3 2024
Statut: epublish

Résumé

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

Identifiants

DOI: 10.1038/s41467-024-46024-1 PMID: 38438375
pubmed: 38438375
doi: 10.1038/s41467-024-46024-1
pii: 10.1038/s41467-024-46024-1
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1960

Subventions

Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : DFG ZI1382/4-1
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)
ID : R01AI170965

Informations de copyright

© 2024. The Author(s).

Références

Arnon, T. I., Horton, R. M., Grigorova, I. L. & Cyster, J. G. Visualization of splenic marginal zone B-cell shuttling and follicular B-cell egress. Nature 493, 684–688 (2013).
pubmed: 23263181 doi: 10.1038/nature11738
Martin, F., Oliver, A. M. & Kearney, J. F. Marginal zone and B1 B cells unite in the early response against T-independent blood-borne particulate antigens. Immunity 14, 617–629 (2001).
pubmed: 11371363 doi: 10.1016/S1074-7613(01)00129-7
Cerutti, A., Cols, M. & Puga, I. Marginal zone B cells: virtues of innate-like antibody-producing lymphocytes. Nat. Rev. Immunol. 13, 118–132 (2013).
pubmed: 23348416 pmcid: 3652659 doi: 10.1038/nri3383
Shlomchik, M. J., Luo, W. & Weisel, F. Linking signaling and selection in the germinal center. Immunol. Rev. 288, 49–63 (2019).
pubmed: 30874353 pmcid: 6422174 doi: 10.1111/imr.12744
Victora, G. D. & Nussenzweig, M. C. Germinal centers. Annu Rev. Immunol. 40, 413–442 (2022).
pubmed: 35113731 doi: 10.1146/annurev-immunol-120419-022408
Pillai, S. & Cariappa, A. The follicular versus marginal zone B lymphocyte cell fate decision. Nat. Rev. Immunol. 9, 767–777 (2009).
pubmed: 19855403 doi: 10.1038/nri2656
Allman, D. et al. Resolution of three nonproliferative immature splenic B cell subsets reveals multiple selection points during peripheral B cell maturation. J. Immunol. 167, 6834–6840 (2001).
pubmed: 11739500 doi: 10.4049/jimmunol.167.12.6834
Martin, F. & Kearney, J. F. Positive selection from newly formed to marginal zone B cells depends on the rate of clonal production, CD19, and btk. Immunity 12, 39–49 (2000).
pubmed: 10661404 doi: 10.1016/S1074-7613(00)80157-0
Agenes, F. & Freitas, A. A. Transfer of small resting B cells into immunodeficient hosts results in the selection of a self-renewing activated B cell population. J. Exp. Med. 189, 319–330 (1999).
pubmed: 9892614 pmcid: 2192996 doi: 10.1084/jem.189.2.319
Cariappa, A. et al. The recirculating B cell pool contains two functionally distinct, long-lived, posttransitional, follicular B cell populations. J. Immunol. 179, 2270–2281 (2007).
pubmed: 17675488 doi: 10.4049/jimmunol.179.4.2270
Gomez Atria, D. et al. Stromal Notch ligands foster lymphopenia-driven functional plasticity and homeostatic proliferation of naive B cells. J. Clin. Invest. 132, e158885 (2022).
pubmed: 35579963 pmcid: 9246379 doi: 10.1172/JCI158885
Srivastava, B., Quinn, W. J. 3rd, Hazard, K., Erikson, J. & Allman, D. Characterization of marginal zone B cell precursors. J. Exp. Med. 202, 1225–1234 (2005).
pubmed: 16260487 pmcid: 2213231 doi: 10.1084/jem.20051038
Vinuesa, C. G. et al. Recirculating and germinal center B cells differentiate into cells responsive to polysaccharide antigens. Eur. J. Immunol. 33, 297–305 (2003).
pubmed: 12548560 doi: 10.1002/immu.200310003
Lechner, M. et al. Notch2-mediated plasticity between marginal zone and follicular B cells. Nat. Commun. 12, 1111 (2021).
pubmed: 33597542 pmcid: 7889629 doi: 10.1038/s41467-021-21359-1
Hampel, F. et al. CD19-independent instruction of murine marginal zone B-cell development by constitutive Notch2 signaling. Blood 118, 6321–6331 (2011).
pubmed: 21795747 doi: 10.1182/blood-2010-12-325944
Hozumi, K. et al. Delta-like 1 is necessary for the generation of marginal zone B cells but not T cells in vivo. Nat. Immunol. 5, 638–644 (2004).
pubmed: 15146182 doi: 10.1038/ni1075
Saito, T. et al. Notch2 is preferentially expressed in mature B cells and indispensable for marginal zone B lineage development. Immunity 18, 675–685 (2003).
pubmed: 12753744 doi: 10.1016/S1074-7613(03)00111-0
Besseyrias, V. et al. Hierarchy of Notch-Delta interactions promoting T cell lineage commitment and maturation. J. Exp. Med. 204, 331–343 (2007).
pubmed: 17261636 pmcid: 2118717 doi: 10.1084/jem.20061442
Tan, J. B. et al. Lunatic and manic fringe cooperatively enhance marginal zone B cell precursor competition for delta-like 1 in splenic endothelial niches. Immunity 30, 254–263 (2009).
pubmed: 19217325 doi: 10.1016/j.immuni.2008.12.016
Fasnacht, N. et al. Specific fibroblastic niches in secondary lymphoid organs orchestrate distinct Notch-regulated immune responses. J. Exp. Med. 211, 2265–2279 (2014).
pubmed: 25311507 pmcid: 4203954 doi: 10.1084/jem.20132528
Lopes-Carvalho, T. & Kearney, J. F. Development and selection of marginal zone B cells. Immunol. Rev. 197, 192–205 (2004).
pubmed: 14962196 doi: 10.1111/j.0105-2896.2004.0112.x
Hammad, H. et al. Transitional B cells commit to marginal zone B cell fate by Taok3-mediated surface expression of ADAM10. Nat. Immunol. 18, 313–320 (2017).
pubmed: 28068307 doi: 10.1038/ni.3657
Cox, E. M. et al. AKT activity orchestrates marginal zone B cell development in mice and humans. Cell Rep. 42, 112378 (2023).
pubmed: 37060566 doi: 10.1016/j.celrep.2023.112378
Nowotschin, S., Xenopoulos, P., Schrode, N. & Hadjantonakis, A. K. A bright single-cell resolution live imaging reporter of Notch signaling in the mouse. BMC Dev. Biol. 13, 15 (2013).
pubmed: 23617465 pmcid: 3663770 doi: 10.1186/1471-213X-13-15
Valls, E. et al. BCL6 antagonizes NOTCH2 to maintain survival of human follicular lymphoma cells. Cancer Discov. 7, 506–521 (2017).
pubmed: 28232365 pmcid: 5413414 doi: 10.1158/2159-8290.CD-16-1189
Casola, S. et al. Tracking germinal center B cells expressing germ-line immunoglobulin gamma1 transcripts by conditional gene targeting. Proc. Natl Acad. Sci. USA 103, 7396–7401 (2006).
pubmed: 16651521 pmcid: 1464351 doi: 10.1073/pnas.0602353103
Heger, K. et al. A novel Cre recombinase reporter mouse strain facilitates selective and efficient infection of primary immune cells with adenoviral vectors. Eur. J. Immunol. 45, 1614–1620 (2015).
pubmed: 25787118 doi: 10.1002/eji.201545457
Basso, K. & Dalla-Favera, R. Roles of BCL6 in normal and transformed germinal center B cells. Immunol. Rev. 247, 172–183 (2012).
pubmed: 22500840 doi: 10.1111/j.1600-065X.2012.01112.x
Ochiai, K. et al. Transcriptional regulation of germinal center B and plasma cell fates by dynamical control of IRF4. Immunity 38, 918–929 (2013).
pubmed: 23684984 pmcid: 3690549 doi: 10.1016/j.immuni.2013.04.009
Sciammas, R. et al. An incoherent regulatory network architecture that orchestrates B cell diversification in response to antigen signaling. Mol. Syst. Biol. 7, 495 (2011).
pubmed: 21613984 pmcid: 3130558 doi: 10.1038/msb.2011.25
Simonetti, G. et al. IRF4 controls the positioning of mature B cells in the lymphoid microenvironments by regulating NOTCH2 expression and activity. J. Exp. Med. 210, 2887–2902 (2013).
pubmed: 24323359 pmcid: 3865479 doi: 10.1084/jem.20131026
Gaudette, B. T. et al. Resting innate-like B cells leverage sustained Notch2/mTORC1 signaling to achieve rapid and mitosis-independent plasma cell differentiation. J. Clin. Invest. 131, e151975 (2021).
pubmed: 34473651 pmcid: 8516456 doi: 10.1172/JCI151975
Chan, W. F. et al. Pre-mitotic genome re-organisation bookends the B cell differentiation process. Nat. Commun. 12, 1344 (2021).
pubmed: 33637722 pmcid: 7910489 doi: 10.1038/s41467-021-21536-2
Cinamon, G. et al. Sphingosine 1-phosphate receptor 1 promotes B cell localization in the splenic marginal zone. Nat. Immunol. 5, 713–720 (2004).
pubmed: 15184895 doi: 10.1038/ni1083
Cinamon, G., Zachariah, M. A., Lam, O. M., Foss, F. W. Jr. & Cyster, J. G. Follicular shuttling of marginal zone B cells facilitates antigen transport. Nat. Immunol. 9, 54–62 (2008).
pubmed: 18037889 doi: 10.1038/ni1542
Sakano, D. et al. BCL6 canalizes Notch-dependent transcription, excluding Mastermind-like1 from selected target genes during left-right patterning. Dev. Cell 18, 450–462 (2010).
pubmed: 20230751 pmcid: 2841049 doi: 10.1016/j.devcel.2009.12.023
Shao, X., Liu, X. & Qi, H. A role for Hes1 in constraining germinal center B cell formation. Cell Insight 2, 100078 (2023).
pubmed: 37193067 pmcid: 10134198 doi: 10.1016/j.cellin.2023.100078
Santos, M. A. et al. Notch1 engagement by Delta-like-1 promotes differentiation of B lymphocytes to antibody-secreting cells. Proc. Natl Acad. Sci. USA 104, 15454–15459 (2007).
pubmed: 17878313 pmcid: 2000509 doi: 10.1073/pnas.0702891104
Yoon, S. O., Zhang, X., Berner, P., Blom, B. & Choi, Y. S. Notch ligands expressed by follicular dendritic cells protect germinal center B cells from apoptosis. J. Immunol. 183, 352–358 (2009).
pubmed: 19542446 doi: 10.4049/jimmunol.0803183
Thomas, M. et al. Notch activity synergizes with B-cell-receptor and CD40 signaling to enhance B-cell activation. Blood 109, 3342–3350 (2007).
pubmed: 17179224 doi: 10.1182/blood-2006-09-046698
Roco, J. A. et al. Class-switch recombination occurs infrequently in germinal centers. Immunity 51, 337–50.e7 (2019).
pubmed: 31375460 pmcid: 6914312 doi: 10.1016/j.immuni.2019.07.001
Sundling, C. et al. Positive selection of IgG(+) over IgM(+) B cells in the germinal center reaction. Immunity 54, 988–1001.e5 (2021).
pubmed: 33857421 doi: 10.1016/j.immuni.2021.03.013
Kallies, A. et al. Plasma cell ontogeny defined by quantitative changes in blimp-1 expression. J. Exp. Med. 200, 967–977 (2004).
pubmed: 15492122 pmcid: 2211847 doi: 10.1084/jem.20040973
Shapiro-Shelef, M. et al. Blimp-1 is required for the formation of immunoglobulin secreting plasma cells and pre-plasma memory B cells. Immunity 19, 607–620 (2003).
pubmed: 14563324 doi: 10.1016/S1074-7613(03)00267-X
Shaffer, A. L. et al. Blimp-1 orchestrates plasma cell differentiation by extinguishing the mature B cell gene expression program. Immunity 17, 51–62 (2002).
pubmed: 12150891 doi: 10.1016/S1074-7613(02)00335-7
Calado, D. P. et al. Constitutive canonical NF-kappaB activation cooperates with disruption of BLIMP1 in the pathogenesis of activated B cell-like diffuse large cell lymphoma. Cancer Cell 18, 580–589 (2010).
pubmed: 21156282 pmcid: 3018685 doi: 10.1016/j.ccr.2010.11.024
Mandelbaum, J. et al. BLIMP1 is a tumor suppressor gene frequently disrupted in activated B cell-like diffuse large B cell lymphoma. Cancer Cell 18, 568–579 (2010).
pubmed: 21156281 pmcid: 3030476 doi: 10.1016/j.ccr.2010.10.030
Kang, J. A., Kim, W. S. & Park, S. G. Notch1 is an important mediator for enhancing of B-cell activation and antibody secretion by Notch ligand. Immunology 143, 550–559 (2014).
pubmed: 24913005 pmcid: 4253503 doi: 10.1111/imm.12333
Zhu, G. et al. Both Notch1 and its ligands in B cells promote antibody production. Mol. Immunol. 91, 17–23 (2017).
pubmed: 28863329 doi: 10.1016/j.molimm.2017.08.021
Liu, Y. J., Oldfield, S. & MacLennan, I. C. Memory B cells in T cell-dependent antibody responses colonize the splenic marginal zones. Eur. J. Immunol. 18, 355–362 (1988).
pubmed: 3258564 doi: 10.1002/eji.1830180306
Pape, K. A. et al. Visualization of the genesis and fate of isotype-switched B cells during a primary immune response. J. Exp. Med. 197, 1677–1687 (2003).
pubmed: 12796466 pmcid: 2193962 doi: 10.1084/jem.20012065
Shih, T. A., Meffre, E., Roederer, M. & Nussenzweig, M. C. Role of BCR affinity in T cell dependent antibody responses in vivo. Nat. Immunol. 3, 570–575 (2002).
pubmed: 12021782 doi: 10.1038/ni803
White, H. N. & Meng, Q. H. Recruitment of a distinct but related set of VH sequences into the murine CD21hi/CD23- marginal zone B cell repertoire to that seen in the class-switched antibody response. J. Immunol. 188, 287–293 (2012).
pubmed: 22140260 doi: 10.4049/jimmunol.1101264
Hendricks, J. et al. The formation of mutated IgM memory B cells in rat splenic marginal zones is an antigen dependent process. PLoS ONE 14, e0220933 (2019).
pubmed: 31490967 pmcid: 6730915 doi: 10.1371/journal.pone.0220933
Anderson, S. M., Tomayko, M. M., Ahuja, A., Haberman, A. M. & Shlomchik, M. J. New markers for murine memory B cells that define mutated and unmutated subsets. J. Exp. Med. 204, 2103–2114 (2007).
pubmed: 17698588 pmcid: 2118690 doi: 10.1084/jem.20062571
Gregoire, C. et al. Viral infection engenders bona fide and bystander subsets of lung-resident memory B cells through a permissive mechanism. Immunity 55, 1216–33.e9 (2022).
pubmed: 35768001 pmcid: 9396418 doi: 10.1016/j.immuni.2022.06.002
Siu, J. H. Y. et al. Two subsets of human marginal zone B cells resolved by global analysis of lymphoid tissues and blood. Sci. Immunol. 7, eabm9060 (2022).
pubmed: 35302862 doi: 10.1126/sciimmunol.abm9060
Kibler, A. et al. Systematic memory B cell archiving and random display shape the human splenic marginal zone throughout life. J. Exp. Med. 218, e20201952 (2021).
pubmed: 33538775 pmcid: 7868796 doi: 10.1084/jem.20201952
Scheffler, L. et al. ERK phosphorylation is RAF independent in naive and activated B cells but RAF dependent in plasma cell differentiation. Sci. Signal. 14, eabc1648 (2021).
pubmed: 33975980 doi: 10.1126/scisignal.abc1648
Sperling, S. et al. Chronic CD30 signaling in B cells results in lymphomagenesis by driving the expansion of plasmablasts and B1 cells. Blood 133, 2597–2609 (2019).
pubmed: 30962205 doi: 10.1182/blood.2018880138
Strobl, L. J. Differently expressed genes between Follicular B cells from control (CD19-Cre) and conditional Notch2-KO (Notch2fl/fl x CD19-Cre) mice [Internet]. https://zenodo.org/records/10491127 (2024).
Heng, T. S. & Painter, M. W., Immunological Genome Project C. The Immunological Genome Project: networks of gene expression in immune cells. Nat. Immunol. 9, 1091–1094 (2008).
pubmed: 18800157 doi: 10.1038/ni1008-1091
Rane, S. Notch2 controls developmental fate choices between germinal center and marginal zone B cells upon immunization [Internet]. https://zenodo.org/records/10475721 (2024).
Ehrenberg, S. Notch2 signalling in B cell activation, immune response and lymphomagenesis [Doctoral thesis] (Ludwig-Maximilians-Universität München, 2014).

Auteurs

Tea Babushku (T)

Research Unit Gene Vectors, Research Group B Cell Development and Activation, Helmholtz Zentrum München, German Research Center for Environmental Health, Feodor-Lynen-Str. 21, D-81377, Munich, Germany.
TranslaTUM, Center for Translational Cancer Research, Technical University of Munich, Einsteinstraße 25, D-81675, Munich, Germany.
ORCID: 0000-0002-4958-361X

Markus Lechner (M)

Research Unit Gene Vectors, Research Group B Cell Development and Activation, Helmholtz Zentrum München, German Research Center for Environmental Health, Feodor-Lynen-Str. 21, D-81377, Munich, Germany.

Stefanie Ehrenberg (S)

Research Unit Gene Vectors, Research Group B Cell Development and Activation, Helmholtz Zentrum München, German Research Center for Environmental Health, Feodor-Lynen-Str. 21, D-81377, Munich, Germany.

Ursula Rambold (U)

Institute of Asthma and Allergy Prevention, Helmholtz Zentrum München, German Research Center for Environmental Health, Feodor-Lynen-Str. 21, D-81377, Munich, Germany.
ORCID: 0009-0006-7112-0749

Marc Schmidt-Supprian (M)

TranslaTUM, Center for Translational Cancer Research, Technical University of Munich, Einsteinstraße 25, D-81675, Munich, Germany.
ORCID: 0000-0002-8543-6166

Andrew J Yates (AJ)

Department of Pathology and Cell Biology, Columbia University Irving Medical Center, 630 West 168th Street, New York, NY, 10032, USA.

Sanket Rane (S)

Irving Institute for Cancer Dynamics, Columbia University, 1190 Amsterdam Ave, New York, 10027, USA.

Ursula Zimber-Strobl (U)

Research Unit Gene Vectors, Research Group B Cell Development and Activation, Helmholtz Zentrum München, German Research Center for Environmental Health, Feodor-Lynen-Str. 21, D-81377, Munich, Germany. strobl@helmholtz-muenchen.de.
Institute of Lung Health and Immunity (LHI), Helmholtz Munich, Comprehensive Pneumology Center (CPC-M), Member of the German Center for Lung Research (DZL), Ingolstädter Landstraße 1, 85764, Neuherberg, Germany. strobl@helmholtz-muenchen.de.
ORCID: 0000-0002-9765-5251

Lothar J Strobl (LJ)

Research Unit Gene Vectors, Research Group B Cell Development and Activation, Helmholtz Zentrum München, German Research Center for Environmental Health, Feodor-Lynen-Str. 21, D-81377, Munich, Germany.
Institute of Lung Health and Immunity (LHI), Helmholtz Munich, Comprehensive Pneumology Center (CPC-M), Member of the German Center for Lung Research (DZL), Ingolstädter Landstraße 1, 85764, Neuherberg, Germany.
ORCID: 0000-0001-8389-1862

Classifications MeSH