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.
Plasmodium falciparum–specific IgM B cells dominate in children, expand with malaria, and produce functional IgM
Disclosures: The authors declare no competing interests exist.
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Christine S. Hopp, Padmapriya Sekar, Ababacar Diouf, Kazutoyo Miura, Kristin Boswell, Jeff Skinner, Christopher M. Tipton, Mary E. Peterson, Michael J. Chambers, Sarah Andrews, Jinghua Lu, Joshua Tan, Shanping Li, Safiatou Doumbo, Kassoum Kayentao, Aissata Ongoiba, Boubacar Traore, Silvia Portugal, Peter D. Sun, Carole Long, Richard A. Koup, Eric O. Long, Adrian B. McDermott, Peter D. Crompton; Plasmodium falciparum–specific IgM B cells dominate in children, expand with malaria, and produce functional IgM. J Exp Med 5 April 2021; 218 (4): e20200901. doi: https://doi.org/10.1084/jem.20200901
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