Engineered B cells expressing an anti-HIV antibody enable memory retention, isotype switching and clonal expansion
| Autor: | Miriam Horovitz-Fried, Tal Akriv, Yariv Wine, Nahmad Ad, David Burstein, Daniel Nataf, Ilan Sofer, Itai Benhar, Adi Barzel, Yuval Raviv, Yaron Carmi, Iris Dotan |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Science medicine.medical_treatment Adaptive immunity General Physics and Astronomy Mice Transgenic HIV Antibodies Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Antigen medicine Animals lcsh:Science AIDS Vaccines B-Lymphocytes Multidisciplinary biology Antibody titer Antibodies Monoclonal virus diseases Germinal center General Chemistry Immunotherapy Acquired immune system Virology 3. Good health Immunoglobulin Isotypes Mice Inbred C57BL 030104 developmental biology Immunoglobulin class switching Immunization 030220 oncology & carcinogenesis Mutation biology.protein lcsh:Q Antibody Genetic Engineering Immunologic Memory Broadly Neutralizing Antibodies |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-10 (2020) Nature Communications |
| ISSN: | 2041-1723 |
| 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) 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. Chronic antiretroviral therapy does not eradicate HIV infection. Here, the authors describe a potentially one-shot alternative by engineering B cells to express anti-HIV antibodies and undergo memory retention, isotype switching and clonal expansion |
| Databáze: | OpenAIRE |
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