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Ex vivo engineered human plasma cells exhibit robust protein secretion and long-term engraftment in vivo

Author

Listed:
  • Rene Yu-Hong Cheng

    (Seattle Children Research Institute
    University of Washington)

  • King L. Hung

    (Seattle Children Research Institute
    Stanford University School of Medicine)

  • Tingting Zhang

    (Seattle Children Research Institute)

  • Claire M. Stoffers

    (Seattle Children Research Institute)

  • Andee R. Ott

    (Seattle Children Research Institute)

  • Emmaline R. Suchland

    (Seattle Children Research Institute)

  • Nathan D. Camp

    (Seattle Children Research Institute)

  • Iram F. Khan

    (Seattle Children Research Institute)

  • Swati Singh

    (Seattle Children Research Institute)

  • Ying-Jen Yang

    (University of Washington)

  • David J. Rawlings

    (Seattle Children Research Institute
    University of Washington
    University of Washington)

  • Richard G. James

    (Seattle Children Research Institute
    University of Washington
    University of Washington
    University of Washington)

Abstract

Due to their unique longevity and capacity to secrete high levels of protein, plasma B cells have the potential to be used as a cell therapy for protein replacement. Here, we show that ex vivo engineered human plasma cells exhibit single-cell RNA profiles, scanning electron micrograph ultrastructural features, and in vivo homing capacity of long-lived plasma cells. After transferring human plasma cells to immunodeficient mice in the presence of the human cytokines BAFF and IL-6, we observe increases in retention of plasma cells in the bone marrow, with engraftment exceeding a year. The most profound in vivo effects of human IL-6 are observed within 20 days of transfer and could be explained by decreased apoptosis in newly differentiated plasma cells. Collectively, these results show that ex vivo engineered and differentiated human plasma cells have the potential for long-lived in vivo protein secretion, which can be modeled in small animals.

Suggested Citation

  • Rene Yu-Hong Cheng & King L. Hung & Tingting Zhang & Claire M. Stoffers & Andee R. Ott & Emmaline R. Suchland & Nathan D. Camp & Iram F. Khan & Swati Singh & Ying-Jen Yang & David J. Rawlings & Richar, 2022. "Ex vivo engineered human plasma cells exhibit robust protein secretion and long-term engraftment in vivo," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33787-8
    DOI: 10.1038/s41467-022-33787-8
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    References listed on IDEAS

    as
    1. Deli Huang & Jenny Tuyet Tran & Alex Olson & Thomas Vollbrecht & Mary Tenuta & Mariia V. Guryleva & Roberta P. Fuller & Torben Schiffner & Justin R. Abadejos & Lauren Couvrette & Tanya R. Blane & Kare, 2020. "Author Correction: Vaccine elicitation of HIV broadly neutralizing antibodies from engineered B cells," Nature Communications, Nature, vol. 11(1), pages 1-1, December.
    2. Deli Huang & Jenny Tuyet Tran & Alex Olson & Thomas Vollbrecht & Mary Tenuta & Mariia V. Guryleva & Roberta P. Fuller & Torben Schiffner & Justin R. Abadejos & Lauren Couvrette & Tanya R. Blane & Kare, 2020. "Vaccine elicitation of HIV broadly neutralizing antibodies from engineered B cells," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    3. Erika Hammarlund & Archana Thomas & Ian J. Amanna & Lindsay A. Holden & Ov D. Slayden & Byung Park & Lina Gao & Mark K. Slifka, 2017. "Plasma cell survival in the absence of B cell memory," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
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    Cited by:

    1. Rene Yu-Hong Cheng & Joseph de Rutte & Cade Ellis K. Ito & Andee R. Ott & Lucie Bosler & Wei-Ying Kuo & Jesse Liang & Brian E. Hall & David J. Rawlings & Dino Di Carlo & Richard G. James, 2023. "SEC-seq: association of molecular signatures with antibody secretion in thousands of single human plasma cells," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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