Plasmodium falciparum–specific IgM B cells dominate in children, expand with malaria, and produce functional IgM
Open Access
- 4 March 2021
- journal article
- research article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 218 (4)
- https://doi.org/10.1084/jem.20200901
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.Funding Information
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases
- National Institutes of Health
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