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

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. Clinical Trials Registration. NCT01624961, NCT02115516, and NCT02237586.