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

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 () and Richard G. James ()
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Rene Yu-Hong Cheng: Seattle Children Research Institute
King L. Hung: Seattle Children Research Institute
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
Richard G. James: Seattle Children Research Institute

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-33787-8

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