B cells engineered to express an anti-HIV antibody allow memory retention, class switch recombination and clonal selection in mice
| Autor: | Yariv Wine, Horovitz-Fried M, Itai Benhar, Sofer I, David Burstein, Nahmad Ad, Yuval Raviv, Iris Dotan, Daniel Nataf, Adi Barzel, Tal Akriv |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0303 health sciences
biology Antibody titer Germinal center Spleen Viremia medicine.disease Virology 3. Good health 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure Immunoglobulin class switching Immunization Antigen 030220 oncology & carcinogenesis biology.protein medicine Antibody 030304 developmental biology |
| DOI: | 10.1101/2020.02.28.970822 |
| Popis: | 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) were shown capable of secreting high antibody titers. Here, we demonstrate 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 higher affinity antigen increases accumulation in GCs and CSR rates. Boost immunization increases rates 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. B cells may thus be engineered as a living and evolving drug. |
| Databáze: | OpenAIRE |
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