IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-27477-0.html
   My bibliography  Save this article

The concerted change in the distribution of cell cycle phases and zone composition in germinal centers is regulated by IL-21

Author

Listed:
  • Dimitra Zotos

    (Monash University)

  • Isaak Quast

    (Monash University)

  • Connie S. N. Li-Wai-Suen

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melboure)

  • Craig I. McKenzie

    (Monash University)

  • Marcus J. Robinson

    (Monash University)

  • Andrey Kan

    (The Walter and Eliza Hall Institute of Medical Research
    University of Adelaide)

  • Gordon K. Smyth

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melboure)

  • Philip D. Hodgkin

    (The Walter and Eliza Hall Institute of Medical Research)

  • David M. Tarlinton

    (Monash University)

Abstract

Humoral immune responses require germinal centres (GC) for antibody affinity maturation. Within GC, B cell proliferation and mutation are segregated from affinity-based positive selection in the dark zone (DZ) and light zone (LZ) substructures, respectively. While IL-21 is known to be important in affinity maturation and GC maintenance, here we show it is required for both establishing normal zone representation and preventing the accumulation of cells in the G1 cell cycle stage in the GC LZ. Cell cycle progression of DZ B cells is unaffected by IL-21 availability, as is the zone phenotype of the most highly proliferative GC B cells. Collectively, this study characterises the development of GC zones as a function of time and B cell proliferation and identifies IL-21 as an important regulator of these processes. These data help explain the requirement for IL-21 in normal antibody affinity maturation.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27477-0
    DOI: 10.1038/s41467-021-27477-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-27477-0
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-27477-0?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. Christoph Jandl & Sue M. Liu & Pablo F. Cañete & Joanna Warren & William E. Hughes & Alexis Vogelzang & Kylie Webster & Maria E. Craig & Gulbu Uzel & Alexander Dent & Polina Stepensky & Bärbel Keller , 2017. "IL-21 restricts T follicular regulatory T cell proliferation through Bcl-6 mediated inhibition of responsiveness to IL-2," Nature Communications, Nature, vol. 8(1), pages 1-14, April.
    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. Takuya Nojima & Kei Haniuda & Tatsuya Moutai & Moeko Matsudaira & Sho Mizokawa & Ikuo Shiratori & Takachika Azuma & Daisuke Kitamura, 2011. "In-vitro derived germinal centre B cells differentially generate memory B or plasma cells in vivo," Nature Communications, Nature, vol. 2(1), pages 1-11, September.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Sophie Hillion & Anjelica Miranda & Christelle Dantec & Marina Boudigou & Laëtitia Pottier & Divi Cornec & Raul M. Torres & Roberta Pelanda, 2024. "Maf expression in B cells restricts reactive plasmablast and germinal center B cell expansion," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. 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.

    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. Marta Iborra-Pernichi & Jonathan Ruiz García & María Velasco de la Esperanza & Belén S. Estrada & Elena R. Bovolenta & Claudia Cifuentes & Cristina Prieto Carro & Tamara González Martínez & José Garcí, 2024. "Defective mitochondria remodelling in B cells leads to an aged immune response," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    2. 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.
    3. Eileen Rauch & Timm Amendt & Aleksandra Lopez Krol & Fabian B. Lang & Vincent Linse & Michelle Hohmann & Ann-Christin Keim & Susanne Kreutzer & Kevin Kawengian & Malte Buchholz & Philipp Duschner & Sa, 2024. "T-bet+ B cells are activated by and control endogenous retroviruses through TLR-dependent mechanisms," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    4. Jianfeng Wu & Kang Yang & Shaowei Cai & Xiaohan Zhang & Lichen Hu & Fanjia Lin & Su-qin Wu & Changchun Xiao & Wen-Hsien Liu & Jiahuai Han, 2022. "A p38α-BLIMP1 signalling pathway is essential for plasma cell differentiation," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    5. Clara Cousu & Eléonore Mulot & Annie Smet & Sara Formichetti & Damiana Lecoeuche & Jianke Ren & Kathrin Muegge & Matthieu Boulard & Jean-Claude Weill & Claude-Agnès Reynaud & Sébastien Storck, 2023. "Germinal center output is sustained by HELLS-dependent DNA-methylation-maintenance in B cells," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    6. 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.
    7. Marina A. Schapfl & Gina M. LoMastro & Vincent Z. Braun & Maretoshi Hirai & Michelle S. Levine & Eva Kiermaier & Verena Labi & Andrew J. Holland & Andreas Villunger, 2024. "Centrioles are frequently amplified in early B cell development but dispensable for humoral immunity," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    8. Ines C. Osma-Garcia & Dunja Capitan-Sobrino & Mailys Mouysset & Sarah E. Bell & Manuel Lebeurrier & Martin Turner & Manuel D. Diaz-Muñoz, 2021. "The RNA-binding protein HuR is required for maintenance of the germinal centre response," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    9. Liat Stoler-Barak & Ethan Harris & Ayelet Peres & Hadas Hezroni & Mirela Kuka & Pietro Lucia & Amalie Grenov & Neta Gurwicz & Meital Kupervaser & Bon Ham Yip & Matteo Iannacone & Gur Yaari & John D. C, 2023. "B cell class switch recombination is regulated by DYRK1A through MSH6 phosphorylation," Nature Communications, Nature, vol. 14(1), pages 1-15, 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:12:y:2021:i:1:d:10.1038_s41467-021-27477-0. 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.