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

ABSTRACT: 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.

SUBMITTER: Hopp CS

PROVIDER: S-EPMC7938365 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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

Hopp Christine S CS Sekar Padmapriya P Diouf Ababacar A Miura Kazutoyo K Boswell Kristin K Skinner Jeff J Tipton Christopher M CM Peterson Mary E ME Chambers Michael J MJ Andrews Sarah S Lu Jinghua J Tan Joshua J Li Shanping S Doumbo Safiatou S Kayentao Kassoum K Ongoiba Aissata A Traore Boubacar B Portugal Silvia S Sun Peter D PD Long Carole C Koup Richard A RA Long Eric O EO McDermott Adrian B AB Crompton Peter D PD

The Journal of experimental medicine 20210401 4

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 adultho ...[more]

PMID: 33661303

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Dataset Information

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

Publications

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

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