Open AccessPlasmodium falciparum–specific IgM B cells dominate in children, expand with malaria, and produce functional IgM
Author(s) -
Christine S. Hopp,
Padmapriya Sekar,
Ababacar Diouf,
Kazutoyo Miura,
Kristin L. Boswell,
Jeff Skinner,
Christopher Tipton,
Mary Peterson,
Michael Chambers,
Sarah F. Andrews,
Jinghua Lu,
Joshua Tan,
Shanping Li,
Safiatou Doumbo,
Kassoum Kayentao,
Aïssata Ongoïba,
Boubacar Traoré,
Sílvia Portugal,
Peter D. Sun,
Carole A. Long,
Richard A. Koup,
Eric O. Long,
Adrian B. McDermott,
Peter D. Crompton
Publication year - 2021
Publication title -
the journal of experimental medicine/the journal of experimental medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.483
H-Index - 448
eISSN - 1540-9538
pISSN - 0022-1007
DOI - 10.1084/jem.20200901
Subject(s) - malaria , biology , immunology , plasmodium falciparum , antibody , immunoglobulin m , phagocytosis , virology , immunoglobulin g , immunity , humoral immunity , opsonin , b cell , immune system
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.