Malaria exposure history shapes PD-1 expression across human B-cell subsets during acute Plasmodium falciparum infection.

BACKGROUND

Repeated malaria exposure shapes humoral immunity in endemic regions. Programmed cell death protein 1 (PD-1) is an inhibitory immune receptor involved in immune regulation during infection, but its expression across human B-cell subsets during acute malaria, and its relationship to exposure history and antigen specificity, remain poorly defined.

METHODS

PD-1 expression and circulating B-cell subsets were analyzed by flow cytometry in 64 individuals from Uganda and Sweden with different malaria exposure backgrounds, including individuals with acute malaria and healthy controls. PD-1 expression was assessed across major B-cell subsets and compared between P. falciparum-binding and non-binding B cells. Associations with parasitemia and inflammatory markers were also examined.

RESULTS

PD-1 expression was higher across both naïve and memory B-cell subsets during acute malaria in Ugandan individuals with ongoing malaria exposure compared with individuals with imported malaria diagnosed in Sweden. Within memory B-cell populations, PD-1 frequencies were highest on non-class-switched (IgD⁺ and IgM⁺) subsets and on P. falciparum-binding B cells. No differences in PD-1 expression were observed between paired acute and convalescent samples. Associations between PD-1 expression, parasitemia, and inflammatory markers were limited and subset-specific.

CONCLUSIONS

PD-1 expression on B cells during malaria differed according to exposure history and B-cell differentiation state. Broad PD-1 induction during acute malaria was observed only in individuals living in a malaria-endemic setting, and PD-1 expression was enriched among P. falciparum-binding B cells. Together, these findings support a potential role for checkpoint pathways in humoral immune regulation during repeated malaria infections.