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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
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    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.
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    1. 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.

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