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In-vitro derived germinal centre B cells differentially generate memory B or plasma cells in vivo

Author

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  • Takuya Nojima

    (Research Institute for Biological Sciences (RIBS), Tokyo University of Science, Noda, Chiba 278-0022, Japan.)

  • Kei Haniuda

    (Research Institute for Biological Sciences (RIBS), Tokyo University of Science, Noda, Chiba 278-0022, Japan.)

  • Tatsuya Moutai

    (Research Institute for Biological Sciences (RIBS), Tokyo University of Science, Noda, Chiba 278-0022, Japan.)

  • Moeko Matsudaira

    (Research Institute for Biological Sciences (RIBS), Tokyo University of Science, Noda, Chiba 278-0022, Japan.)

  • Sho Mizokawa

    (Research Institute for Biological Sciences (RIBS), Tokyo University of Science, Noda, Chiba 278-0022, Japan.)

  • Ikuo Shiratori

    (Research Institute for Biological Sciences (RIBS), Tokyo University of Science, Noda, Chiba 278-0022, Japan.)

  • Takachika Azuma

    (Research Institute for Biological Sciences (RIBS), Tokyo University of Science, Noda, Chiba 278-0022, Japan. Correspondence and requests for materials should be addressed to D.K. (email: ).)

  • Daisuke Kitamura

    (Research Institute for Biological Sciences (RIBS), Tokyo University of Science, Noda, Chiba 278-0022, Japan.)

Abstract

In response to T cell-dependent antigens, B cells proliferate extensively to form germinal centres (GC), and then differentiate into memory B (Bmem) cells or long-lived plasma cells (LLPCs) by largely unknown mechanisms. Here we show a new culture system in which mouse naïve B cells undergo massive expansion and isotype switching, and generate GC-phenotype B (iGB) cells. The iGB cells expressing IgG1 or IgM/D, but not IgE, differentiate into Bmem cells in vivo after adoptive transfer and can elicit rapid immune responses with the help of cognate T cells. Secondary culture with IL-21 maintains the proliferation of the iGB cells, while shifting their in vivo developmental fate from Bmem cells to LLPCs, an outcome that can be reversed by withdrawal of IL-21 in tertiary cultures. Thus, this system enables in vitro manipulation of B-cell fate, into either Bmem cells or LLPCs, and will facilitate dissection of GC-B cell differentiation programs.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:2:y:2011:i:1:d:10.1038_ncomms1475
    DOI: 10.1038/ncomms1475
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    1. 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.
    2. 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.
    3. 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.
    4. 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.
    5. 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.
    6. 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.
    7. 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.

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