Infection-induced plasmablasts are a nutrient sink that impairs humoral immunity to malaria

Plasmodium parasite-specific antibodies are critical for protection against malaria, yet the development of long-lived and effective humoral immunity against Plasmodium takes many years and multiple rounds of infection and cure. Here we report that the rapid development of short-lived plasmablasts during experimental malaria unexpectedly hindered parasite control by impeding germinal center (GC) responses. Metabolic hyperactivity of plasmablasts resulted in nutrient deprivation of the GC reaction limiting the generation of memory B cell and long-lived plasma cell responses. Therapeutic administration of a single amino acid to experimentally infected mice was sufficient to overcome the metabolic constraints imposed by plasmablasts and enhanced parasite clearance and the formation of protective humoral immune memory responses. Thus, our studies not only challenge the current paradigm describing the role and function of blood-stage Plasmodium-induced plasmablasts, but also reveal new targets and strategies to improve anti-Plasmodium humoral immunity.