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, Adi Barzel
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.