Differences in phenotype between long-lived memory B cells againstPlasmodium falciparummerozoite antigens and variant surface antigens

Plasmodium falciparuminfections elicit strong humoral immune responses to two main groups of antigens expressed by blood-stage parasites: merozoite antigens that are involved in the erythrocyte invasion process and variant surface antigens that mediate endothelial sequestration of infected erythrocytes. Long-lived B cells against both antigen classes can be detected in the circulation for years after exposure, but have not been directly compared. Here, we studied the phenotype of long-lived memory and atypical B cells to merozoite antigens (MSP1 and AMA1) and variant surface antigens (the CIDRα1 domain of PfEMP1) in Ugandan adults before and after local reduction ofP. falciparumtransmission. After a median of 1.7 years withoutP. falciparuminfections, the percentage of antigen-specific activated B cells declined, but long-lived antigen-specific B cells were still detectable in all individuals. The majority of MSP1/AMA1-specific B cells were CD95⁺CD11c⁺memory B cells, which are primed for rapid differentiation into antibody-secreting cells, and FcRL5^-T-bet^-atypical B cells. On the other hand, most CIDRα1-specific B cells were CD95^-CD11c^-memory B cells. CIDRα1-specific B cells were also enriched among a subset of atypical B cells that seem poised for antigen presentation. These results point to differences in how these antigens are recognized or processed by the immune system and howP. falciparum-specific B cells will respond upon re-infection.