期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 218, 期 4, 页码 -出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20200901
关键词
-
资金
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health
In a Mali cohort, IgM antibodies dominate in memory B cells against malaria and expand and activate during malaria infection.
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.
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