Plasmodium falciparum-specific IgM B cells dominate in children, expand with malaria, and produce functional IgM

J Exp Med. 2021 Apr 5;218(4):e20200901. doi: 10.1084/jem.20200901.


IgG antibodies play a role in malaria immunity, but whether and how IgM protects from malaria and the biology of Plasmodium falciparum (Pf)-specific IgM B cells is unclear. In a Mali cohort spanning infants to adults, we conducted longitudinal analyses of Pf- and influenza-specific B cells. We found that Pf-specific memory B cells (MBCs) 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. B cell receptor analysis showed Pf-specific IgM MBCs are somatically hypermutated at levels comparable to influenza-specific IgG B cells. During acute malaria, Pf-specific IgM B cells expand and upregulate activation/costimulatory markers. Finally, plasma IgM was comparable to IgG in inhibiting Pf growth and enhancing phagocytosis of Pf by monocytes in vitro. Thus, somatically hypermutated Pf-specific IgM MBCs dominate in children, expand and activate during malaria, and produce IgM that inhibits Pf through neutralization and opsonic phagocytosis.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Protozoan / blood
  • Antibodies, Protozoan / immunology*
  • Antigens, Protozoan / immunology
  • B-Lymphocytes / immunology*
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology*
  • Immunoglobulin M / blood
  • Immunoglobulin M / immunology*
  • Immunologic Memory
  • Infant
  • Infant, Newborn
  • Longitudinal Studies
  • Malaria / blood
  • Malaria / epidemiology
  • Malaria / immunology*
  • Malaria / parasitology
  • Malaria, Falciparum / blood
  • Malaria, Falciparum / epidemiology
  • Malaria, Falciparum / immunology*
  • Malaria, Falciparum / parasitology
  • Male
  • Mali / epidemiology
  • Phagocytosis / immunology
  • Plasmodium falciparum / immunology*
  • Young Adult


  • Antibodies, Protozoan
  • Antigens, Protozoan
  • Immunoglobulin G
  • Immunoglobulin M

Supplementary concepts

  • Acute malaria