Engineered B cells expressing an anti-HIV antibody enable memory retention, isotype switching and clonal expansion

Alessio D. Nahmad, Yuval Raviv, Miriam Horovitz-Fried, Ilan Sofer, Tal Akriv, Daniel Nataf, Iris Dotan, Yaron Carmi, David Burstein, Yariv Wine, Itai Benhar and Adi Barzel ()
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Alessio D. Nahmad: Tel Aviv University
Yuval Raviv: Tel Aviv University
Miriam Horovitz-Fried: Tel Aviv University
Ilan Sofer: Tel Aviv University
Tal Akriv: Tel Aviv University
Daniel Nataf: Tel Aviv University
Iris Dotan: Tel Aviv University
Yaron Carmi: Tel Aviv University
David Burstein: Tel Aviv University
Yariv Wine: Tel Aviv University
Itai Benhar: Tel Aviv University
Adi Barzel: Tel Aviv University

Nature Communications, 2020, vol. 11, issue 1, 1-10

Abstract: ABSTRACT HIV viremia can be controlled by chronic antiretroviral therapy. As a potentially single-shot alternative, B cells engineered by CRISPR/Cas9 to express anti-HIV broadly neutralizing antibodies (bNAbs) are capable of secreting high antibody titers. Here, we show that, upon immunization of mice, adoptively transferred engineered B cells home to germinal centers (GC) where they predominate over the endogenous response and differentiate into memory and plasma cells while undergoing class switch recombination (CSR). Immunization with a high affinity antigen increases accumulation in GCs and CSR rates. Boost immunization increases the rate of engineered B cells in GCs and antibody secretion, indicating memory retention. Finally, antibody sequences of engineered B cells in the spleen show patterns of clonal selection. Therefore, B cells can be engineered into what could be a living and evolving drug.

Date: 2020
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DOI: 10.1038/s41467-020-19649-1

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