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

• DOI: 10.1038/s41467-017-00645-x
• Publication Date: 2017-09-11T10:13:04Z
• Authors: Ben S. Wendel; Chenfeng He; Mingjuan Qu; Di Wu; Stefany M. Hernandez; Ke-Yue Ma; Eugene W. Liu; Jun Xiao; Peter D. Crompton; Susan K. Pierce; Pengyu Ren; Keke Chen; Ning Jiang
• Keywords: 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

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.