Plasmodium falciparum-specific IgM B cells responses to natural malaria infection in children and adults | New Voices in Infection Biology

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Talk abstract:

Plasmodium falciparum malaria kills more than 400,000 people annually, and a highly effective vaccine remains elusive. Although IgG antibodies are known to play a role in immunity to malaria, little is known about the IgM response to malaria, the mechanisms by which IgM may protect, or the underlying biology of P. falciparum-specific IgM B cells. In a Mali cohort spanning infants to adults, we conducted a longitudinal analysis of both P. falciparum-specific and influenza-specific B cells. Surprisingly, we found that P. falciparum-specific memory B cells (MBCs) in children are disproportionally IgM+ and only gradually shift to IgG+ with age, in contrast to influenza-specific MBCs that are predominantly IgG+ from infancy to adulthood—indicating differential isotype switch rates for P. falciparum-specific B cells that may have implications for vaccine efforts. Notably, we found in children that P. falciparum-specific IgM MBCs are activated and expand during acute malaria infection and produce IgM that is superior to IgG in promoting opsonic phagocytosis of blood-stage parasites by monocytes, indicating that IgM-dominated responses in children may contribute to early protection from lethal malaria. Finally, B cell receptor analysis showed that P. falciparum-specific IgM B cells are somatically hypermutated at levels comparable to influenza-specific IgG B cells, suggesting that Plasmodium-specific IgM B cells are bona fide MBCs.