Biology subjects

Crompton, P. D.

Publications and source records attributed to Crompton, P. D..

2 recordsLinked to original sources

bioRxiv2018

NK cells inhibit Plasmodium falciparum growth in red blood cells via antibody dependent cellular cytotoxicity

Antibodies acquired naturally through repeated exposure to Plasmodium falciparum are essential in the control of blood-stage malaria. Antibody-dependent functions may include neutralization of parasite-host interactions, complement activation, and activation of Fc receptor functions. A role of antibody-dependent cellular cytotoxicity (ADCC) by natural killer (NK) cells in protection from malaria has not been established. Here we show that IgG isolated from adults living in a malaria-endemic region activated ADCC by primary human NK cells, which lysed infected red blood cells (RBCs) and inhibited parasite growth in an in vitro assay for ADCC-dependent growth inhibition. RBC lysis by NK cells was highly selective for infected RBCs in a mixed culture with uninfected RBCs. Human antibodies to P. falciparum antigens PfEMP1 and RIFIN were sufficient to promote NK-dependent growth inhibition. As these results implicate acquired immunity through NK-mediated ADCC, antibody-based vaccines that target bloodstream parasites should consider this new mechanism of action.

immunology↗

bioRxiv2017

Accurate Immune Repertoire Sequencing Reveals Malaria Infection Driven Antibody Lineage Diversification in Young Children

Accurately measuring antibody repertoire sequence composition in a small amount of blood is challenging yet important to the understanding of the repertoire response to infections and vaccinations. Here, we describe an accurate and high-coverage repertoire sequencing method, MIDCIRS, which uses as few as 1,000 naive B cells. Using it, we studied 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 draws. Unexpectedly, we discovered high levels of somatic hypermutation (SHM) in infants as young as three months old. Antibody clonal lineage analysis revealed that both infants and toddlers increase SHM levels upon infection and memory B cells isolated from pre-malaria samples in malaria-experienced individuals continue to induce SHMs upon malaria rechallenge. These results highlight the vast potential of antibody repertoire diversification in infants and toddlers that has not been realized previously.

immunology↗