# Effect of controlled human Plasmodium falciparum infection on B cell subsets in individuals with different levels of malaria immunity

## TL;DR

The study shows how malaria infection affects different types of B cells in people with varying levels of immunity, including those who are vaccinated or naturally exposed.

## Contribution

The study reveals how malaria immunity and vaccination influence B cell subset frequencies and how CHMI modulates these effects.

## Key findings

- Semi-immune individuals had higher baseline frequencies of immature and active B cell subsets compared to malaria-naïve individuals.
- CHMI caused an expansion of resting classical memory B cells in all groups during early infection.
- Vaccination altered the effect of CHMI on B cells, with specific associations observed for resting classical memory B cells and active naïve B cells.

## Abstract

Continuous exposure to Plasmodium falciparum (Pf) has been associated with alterations in B cells. We investigated the effect of controlled human malaria infection (CHMI) on B cell phenotypes in individuals with different Pf immunity status: malaria-naïve, immunized with PfSPZ-CVac and semi-immune (lifelong-exposed) volunteers. Compared to naïve, semi-immune but not vaccinated individuals, had increased baseline frequencies of immature B cells (CD19+CD10+), active naive (IgD+CD27−CD21−) B cells, active atypical (IgD−CD27−CD21−) memory B cells (MBCs), active classical (IgD−CD27+CD21−) MBCs and CD1c+-B cells but lower frequencies of some IgG+-B cells. The frequencies of CD1c+ active atypical MBCs correlated positively with anti-Pf antibodies and negatively with circulating eotaxin levels, while the opposite was observed for IgG+ resting atypical MBCs. During early blood-stage infection (day 11 after CHMI), there was an expansion of resting classical (IgD−CD27+CD21+) MBCs in all three groups. Vaccination, compared to placebo, altered the effect of CHMI on B cells, showing a positive association with resting classical MBCs (β = 0.190, 95%CI 0.011–0.368) and active naïve-PD1+ (β = 0.637, 95%CI 0.058–1.217) frequencies, and a negative one with CD1c+ resting atypical MBCs (β=−0.328, 95%CI −0.621–−0.032). In addition, the sickle cell trait in semi-immune subjects altered the effect of CHMI on several B cells. In conclusion, lifelong but not vaccine exposure to malaria was associated with increased frequencies of multiple B cell subsets, with higher and lower percentages of CD1c and IgG expressing-cells, respectively. A single infection (CHMI) induces changes in B cell frequencies and is modulated by sickle cell trait and malaria-immunity status.