IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-41880-9.html
   My bibliography  Save this article

Continually recruited naïve T cells contribute to the follicular helper and regulatory T cell pools in germinal centers

Author

Listed:
  • Julia Merkenschlager

    (The Rockefeller University)

  • Riza-Maria Berz

    (The Rockefeller University)

  • Victor Ramos

    (The Rockefeller University)

  • Maximilian Uhlig

    (The Rockefeller University)

  • Andrew J. MacLean

    (The Rockefeller University)

  • Carla R. Nowosad

    (New York University Grossman School of Medicine)

  • Thiago Y. Oliveira

    (The Rockefeller University)

  • Michel C. Nussenzweig

    (The Rockefeller University
    The Rockefeller University)

Abstract

Follicular helper T cells (TFH) mediate B cell selection and clonal expansion in germinal centers (GCs), and follicular regulatory T cells (TFR) prevent the emergence of self-reactive B cells and help to extinguish the reaction. Here we show that GC reactions continually recruit T cells from both the naïve conventional and naive thymic regulatory T cell (Treg) repertoires. In the early GC, newly recruited T cells develop into TFH, whereas cells entering during the contraction phase develop into TFR cells that contribute to GC dissolution. The TFR fate decision is associated with decreased antigen availability and is modulated by slow antigen delivery or mRNA vaccination. Thus, invasion of ongoing GCs by newly developing TFH and TFR helps remodel the GC based on antigen availability.

Suggested Citation

  • Julia Merkenschlager & Riza-Maria Berz & Victor Ramos & Maximilian Uhlig & Andrew J. MacLean & Carla R. Nowosad & Thiago Y. Oliveira & Michel C. Nussenzweig, 2023. "Continually recruited naïve T cells contribute to the follicular helper and regulatory T cell pools in germinal centers," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41880-9
    DOI: 10.1038/s41467-023-41880-9
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-41880-9
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-41880-9?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Jackson S. Turner & Jane A. O’Halloran & Elizaveta Kalaidina & Wooseob Kim & Aaron J. Schmitz & Julian Q. Zhou & Tingting Lei & Mahima Thapa & Rita E. Chen & James Brett Case & Fatima Amanat & Adriana, 2021. "SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses," Nature, Nature, vol. 596(7870), pages 109-113, August.
    2. Alexander D. Gitlin & Ziv Shulman & Michel C. Nussenzweig, 2014. "Clonal selection in the germinal centre by regulated proliferation and hypermutation," Nature, Nature, vol. 509(7502), pages 637-640, May.
    3. Facundo D. Batista & Dagmar Iber & Michael S. Neuberger, 2001. "B cells acquire antigen from target cells after synapse formation," Nature, Nature, vol. 411(6836), pages 489-494, May.
    4. Meryem Aloulou & Edward J. Carr & Mylène Gador & Alexandre Bignon & Roland S. Liblau & Nicolas Fazilleau & Michelle A. Linterman, 2016. "Follicular regulatory T cells can be specific for the immunizing antigen and derive from naive T cells," Nature Communications, Nature, vol. 7(1), pages 1-10, April.
    5. Julia Merkenschlager & Shlomo Finkin & Victor Ramos & Julian Kraft & Melissa Cipolla & Carla R. Nowosad & Harald Hartweger & Wenzhu Zhang & Paul Dominic B. Olinares & Anna Gazumyan & Thiago Y. Oliveir, 2021. "Dynamic regulation of TFH selection during the germinal centre reaction," Nature, Nature, vol. 591(7850), pages 458-463, March.
    6. Julia Merkenschlager & Mickaël J. Ploquin & Urszula Eksmond & Rakieb Andargachew & Georgina Thorborn & Andrew Filby & Marion Pepper & Brian Evavold & George Kassiotis, 2016. "Stepwise B-cell-dependent expansion of T helper clonotypes diversifies the T-cell response," Nature Communications, Nature, vol. 7(1), pages 1-13, April.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Ankita Leekha & Arash Saeedi & Monish Kumar & K. M. Samiur Rahman Sefat & Melisa Martinez-Paniagua & Hui Meng & Mohsen Fathi & Rohan Kulkarni & Kate Reichel & Sujit Biswas & Daphne Tsitoura & Xinli Li, 2024. "An intranasal nanoparticle STING agonist protects against respiratory viruses in animal models," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    2. Dimitra Zotos & Isaak Quast & Connie S. N. Li-Wai-Suen & Craig I. McKenzie & Marcus J. Robinson & Andrey Kan & Gordon K. Smyth & Philip D. Hodgkin & David M. Tarlinton, 2021. "The concerted change in the distribution of cell cycle phases and zone composition in germinal centers is regulated by IL-21," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    3. Hassen Kared & Asia-Sophia Wolf & Amin Alirezaylavasani & Anthony Ravussin & Guri Solum & Trung The Tran & Fridtjof Lund-Johansen & John Torgils Vaage & Lise Sofie Nissen-Meyer & Unni C. Nygaard & Ola, 2022. "Immune responses in Omicron SARS-CoV-2 breakthrough infection in vaccinated adults," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    4. Emanuele Andreano & Ida Paciello & Silvia Marchese & Lorena Donnici & Giulio Pierleoni & Giulia Piccini & Noemi Manganaro & Elisa Pantano & Valentina Abbiento & Piero Pileri & Linda Benincasa & Ginevr, 2022. "Anatomy of Omicron BA.1 and BA.2 neutralizing antibodies in COVID-19 mRNA vaccinees," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    5. Vincent Pavot & Catherine Berry & Michael Kishko & Natalie G. Anosova & Lu Li & Tim Tibbitts & Dean Huang & Alice Raillard & Sylviane Gautheron & Cindy Gutzeit & Marguerite Koutsoukos & Roman M. Chicz, 2023. "Beta variant COVID-19 protein booster vaccine elicits durable cross-neutralization against SARS-CoV-2 variants in non-human primates," Nature Communications, Nature, vol. 14(1), pages 1-8, December.
    6. Jernej Pušnik & Jasmin Zorn & Werner O. Monzon-Posadas & Kathrin Peters & Emmanuil Osypchuk & Sabine Blaschke & Hendrik Streeck, 2024. "Vaccination impairs de novo immune response to omicron breakthrough infection, a precondition for the original antigenic sin," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    7. Jonathan D. Worboys & Katherine N. Vowell & Roseanna K. Hare & Ashley R. Ambrose & Margherita Bertuzzi & Michael A. Conner & Florence P. Patel & William H. Zammit & Judit Gali-Moya & Khodor S. Hazime , 2023. "TIGIT can inhibit T cell activation via ligation-induced nanoclusters, independent of CD226 co-stimulation," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    8. Hyun Jae Lee & Marcela L. Moreira & Shihan Li & Takahiro Asatsuma & Cameron G. Williams & Oliver P. Skinner & Saba Asad & Michael Bramhall & Zhe Jiang & Zihan Liu & Ashlyn S. Kerr & Jessica A. Engel &, 2024. "CD4+ T cells display a spectrum of recall dynamics during re-infection with malaria parasites," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    9. Bonnie Huang & James D. Phelan & Silvia Preite & Julio Gomez-Rodriguez & Kristoffer H. Johansen & Hirofumi Shibata & Arthur L. Shaffer & Qin Xu & Brendan Jeffrey & Martha Kirby & Stacie Anderson & Yan, 2022. "In vivo CRISPR screens reveal a HIF-1α-mTOR-network regulates T follicular helper versus Th1 cells," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    10. Arnaud Desrosiers & Rabeb Mouna Derbali & Sami Hassine & Jérémie Berdugo & Valérie Long & Dominic Lauzon & Vincent De Guire & Céline Fiset & Luc DesGroseillers & Jeanne Leblond Chain & Alexis Vallée-B, 2022. "Programmable self-regulated molecular buffers for precise sustained drug delivery," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    11. Ivan T. Lee & Raffael Nachbagauer & David Ensz & Howard Schwartz & Lizbeth Carmona & Kristi Schaefers & Andrei Avanesov & Daniel Stadlbauer & Carole Henry & Ren Chen & Wenmei Huang & Daniela Ramirez S, 2023. "Safety and immunogenicity of a phase 1/2 randomized clinical trial of a quadrivalent, mRNA-based seasonal influenza vaccine (mRNA-1010) in healthy adults: interim analysis," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    12. Thomas Hu & Mayar Allam & Shuangyi Cai & Walter Henderson & Brian Yueh & Aybuke Garipcan & Anton V. Ievlev & Maryam Afkarian & Semir Beyaz & Ahmet F. Coskun, 2023. "Single-cell spatial metabolomics with cell-type specific protein profiling for tissue systems biology," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    13. Leander Witte & Viren A. Baharani & Fabian Schmidt & Zijun Wang & Alice Cho & Raphael Raspe & Camila Guzman-Cardozo & Frauke Muecksch & Marie Canis & Debby J. Park & Christian Gaebler & Marina Caskey , 2023. "Epistasis lowers the genetic barrier to SARS-CoV-2 neutralizing antibody escape," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    14. Zixiang Wang & Shourong Wang & Junchao Qin & Xiyu Zhang & Gang Lu & Hongbin Liu & Haiyang Guo & Ligang Wu & Victoria O. Shender & Changshun Shao & Beihua Kong & Zhaojian Liu, 2022. "Splicing factor BUD31 promotes ovarian cancer progression through sustaining the expression of anti-apoptotic BCL2L12," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    15. Jernej Pušnik & Werner O. Monzon-Posadas & Jasmin Zorn & Kathrin Peters & Maximilian Baum & Hannah Proksch & Celina Beta Schlüter & Galit Alter & Tanja Menting & Hendrik Streeck, 2023. "SARS-CoV-2 humoral and cellular immunity following different combinations of vaccination and breakthrough infection," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    16. Marta Ferreira-Gomes & Yidan Chen & Pawel Durek & Hector Rincon-Arevalo & Frederik Heinrich & Laura Bauer & Franziska Szelinski & Gabriela Maria Guerra & Ana-Luisa Stefanski & Antonia Niedobitek & Ann, 2024. "Recruitment of plasma cells from IL-21-dependent and IL-21-independent immune reactions to the bone marrow," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    17. Laura Pérez-Alós & Jose Juan Almagro Armenteros & Johannes Roth Madsen & Cecilie Bo Hansen & Ida Jarlhelt & Sebastian Rask Hamm & Line Dam Heftdal & Mia Marie Pries-Heje & Dina Leth Møller & Kamille F, 2022. "Modeling of waning immunity after SARS-CoV-2 vaccination and influencing factors," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    18. Eike-Christian Wamhoff & Larance Ronsard & Jared Feldman & Grant A. Knappe & Blake M. Hauser & Anna Romanov & James Brett Case & Shilpa Sanapala & Evan C. Lam & Kerri J. St. Denis & Julie Boucau & Amy, 2024. "Enhancing antibody responses by multivalent antigen display on thymus-independent DNA origami scaffolds," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    19. Hassan N. Althurwi & Khalid M. Alharthy & Faisal F. Albaqami & Ali Altharawi & Muhammad Rizwan Javed & Ziyad Tariq Muhseen & Muhammad Tahir ul Qamar, 2022. "mRNA-Based Vaccine Designing against Epstein-Barr Virus to Induce an Immune Response Using Immunoinformatic and Molecular Modelling Approaches," IJERPH, MDPI, vol. 19(20), pages 1-21, October.
    20. Philipe Gobeil & Stéphane Pillet & Iohann Boulay & Nathalie Charland & Aurélien Lorin & Matthew P. Cheng & Donald C. Vinh & Philippe Boutet & Robbert Most & François Roman & Maria Angeles Ceregido & N, 2022. "Durability and cross-reactivity of immune responses induced by a plant-based virus-like particle vaccine for COVID-19," Nature Communications, Nature, vol. 13(1), pages 1-10, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41880-9. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.