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Abstract
Accurately measuring antibody repertoire sequence composition in a small amount of blood is challenging yet important for understanding repertoire responses to infection and vaccination. We develop molecular identifier clustering-based immune repertoire sequencing (MIDCIRS) and use it to study age-related antibody repertoire development and diversification before and during acute malaria in infants (< 12 months old) and toddlers (12–47 months old) with 4−8 ml of blood. Here, we show this accurate and high-coverage repertoire-sequencing method can use as few as 1000 naive B cells. Unexpectedly, we discover high levels of somatic hypermutation in infants as young as 3 months old. Antibody clonal lineage analysis reveals that somatic hypermutation levels are increased in both infants and toddlers upon infection, and memory B cells isolated from individuals who previously experienced malaria continue to induce somatic hypermutations upon malaria rechallenge. These results highlight the potential of antibody repertoire diversification in infants and toddlers.
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1 McKetta Department of Chemical Engineering, Cockrell School of Engineering, University of Texas at Austin, Austin, TX, USA
2 Department of Biomedical engineering, Cockrell School of Engineering, University of Texas at Austin, Austin, TX, USA
3 Department of Biomedical engineering, Cockrell School of Engineering, University of Texas at Austin, Austin, TX, USA; School of Life Sciences, Ludong University, Yantai, Shandong, China
4 Institute for Cellular and Molecular Biology, College of Natural Sciences, University of Texas at Austin, Austin, TX, USA
5 Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA; Parasitic Diseases Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Atlanta, GA, USA
6 ImmuDX, LLC, Austin, TX, USA
7 Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA
8 Department of Computer Science and Engineering, Wright State University, Dayton, OH, USA
9 Department of Biomedical engineering, Cockrell School of Engineering, University of Texas at Austin, Austin, TX, USA; Institute for Cellular and Molecular Biology, College of Natural Sciences, University of Texas at Austin, Austin, TX, USA