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

作者：Wendel, Ben S.; He, Chenfeng; Qu, Mingjuan; Wu, Di; Hernandez, Stefany M.; Ma, Ke-Yue; Liu, Eugene W.; Xiao, Jun; Crompton, Peter D.; Pierce, Susan K.; Ren, Pengyu; Chen, Keke; Jiang, Ning^*

来源：Nature Communications, 2017, 8(1): 531.

DOI：10.1038/s41467-017-00645-x

• MEMORY B-CELLS
• SOMATIC HYPERMUTATION
• IMMUNOGLOBULIN REPERTOIRE
• PLASMA-CELLS
• GENES
• DIFFERENTIATION
• GENERATION
• LYMPHOCYTES
• POPULATIONS
• MATURATION

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 4-8ml 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.

• 出版日期2017-9-14
• 单位鲁东大学; NIH