A single nucleotide polymorphism in a Plasmodium berghei ApiAP2 transcription factor alters the development of host immunity

Antibodies play a central role in malaria immunity but their acquisition is both remarkably slow and unpredictable. At present we know little about the malaria parasite genesthat influence host immunity. Here we show that a single nucleotide polymorphism (SNP) in thegene encoding an ApiAP2 transcription factor in the rodent malaria parasite Plasmodium berghei(Pb) NK65, resulting in a single amino acid change (a S to F), converted a nonimmunogenicparasite (PbNK65S) to a parasite (PbNK65F) that induced protective immunity. The S to F SNPis unique and has occurred only once in the evolution of Plasmodium namely in the rodentparasite PbANKA. PbNK65F parasites differentially expressed 46 genes, most of which arepredicted to play roles in immune evasion. PbNK65F infections resulted in a large expansion ofgerminal center B cells, plasma cell lineage B cells and T follicular helper cells by a ?-interferondependentprocess resulting in higher levels of infected red blood cell-specific TH1-type IgG2band 2c antibodies. Thus, the Pb ApiAP2 transcription factor functions as a critical parasitevirulence factor in malaria infections.