MIDCIRS Reveals Antibody Diversification in Young Children with Malaria

This study describes a novel Immune Repertoire Sequencing technique, termed Molecular Identifier Clustering-based Immune Repertoire Sequencing (MIDCIRS), to reduce sequencing error while maintaining extremely high coverage and applies this technique to investigate the differential immune response to malaria between infants and toddlers. Despite a lower somatic hypermutation load, we found an unexpectedly high level of competency within the infant antibody repertoire, particularly the ability to diversify B cell clonal lineages upon acute infection. Detailed clonal lineage analysis encompassing lineages containing sequences from both pre- and acute malaria timepoints revealed an increase in somatic hypermutations upon acute infection. Further analysis on pre-malaria memory B cell containing lineages in toddlers who had previously been exposed to malaria provides evidence for the capacity of memory B cells to continue to mutate and isotype switch.]]>
Infant and toddler PBMC samples from 22 residents of Kalifabougou, Mali, ranging from 3 months old to 47 months old, were collected from an ongoing malaria cohort study. Enrollment exclusion criteria were hemoglobin level <7g/dL, axillary temperature >/=37.5°C, acute systemic illness, use of antimalarial or immunosuppressive medications in the past 30 days, and pregnancy. The research definition of malaria was an axillary temperature of >/=37.5°C, >/=2500 asexual parasites/μL of blood, and no other cause of fever discernible by physical exam.]]>