1. Frequency-potency analysis of IgG+ memory B cells delineates neutralizing antibody responses at single-cell resolution
- Author
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Michelle K. Tenggara, Seo-Ho Oh, Catherine Yang, Hardik K. Nariya, Amanda M. Metz, Amit A. Upadhyay, Dedeepya R. Gudipati, Lizheng Guo, Emily G. McGhee, Kiran Gill, Elise G. Viox, Rosemarie D. Mason, Nicole A. Doria-Rose, Kathryn E. Foulds, John R. Mascola, Yuhong Du, Haian Fu, John D. Altman, Qi Yan, Zizhang Sheng, Steven E. Bosinger, and Rui Kong
- Subjects
CP: Immunology ,Biology (General) ,QH301-705.5 - Abstract
Summary: Identifying individual functional B cell receptors (BCRs) is common, but two-dimensional analysis of B cell frequency versus BCR potency would delineate both quantity and quality of antigen-specific memory B cells. We efficiently determine quantitative BCR neutralizing activities using a single-cell-derived antibody supernatant analysis (SCAN) workflow and develop a frequency-potency algorithm to estimate B cell frequencies at various neutralizing activity or binding affinity cutoffs. In an HIV-1 fusion peptide (FP) immunization study, frequency-potency curves elucidate the quantity and quality of FP-specific immunoglobulin G (IgG)+ memory B cells for different animals, time points, and antibody lineages at single-cell resolution. The BCR neutralizing activities are mainly determined by their affinities to soluble envelope trimer. Frequency analysis definitively demonstrates dominant neutralizing antibody lineages. These findings establish SCAN and frequency-potency analyses as promising approaches for general B cell analysis and monoclonal antibody (mAb) discovery. They also provide specific rationales for HIV-1 FP-directed vaccine optimization.
- Published
- 2024
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