Accurate immune repertoire sequencing reveals malaria infection driven antibody lineage diversification in young children

B-Lymphocytes Science Q Infant Sequence Analysis, DNA Mali Article Antibodies V(D)J Recombination Malaria 3. Good health Immunoglobulin M Child, Preschool Humans Somatic Hypermutation, Immunoglobulin Immunologic Memory
DOI: 10.1038/s41467-017-00645-x Publication Date: 2017-09-11T10:13:04Z
ABSTRACT
AbstractAccurately 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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