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

• Authors: Christine S Hopp, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville; Padmapriya Sekar, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville; Ababacar Diouf, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville; Kazutoyo Miura, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville; Kristin Boswell, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville; Jeff Skinner, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville; Christopher Tipton, Emory University; Mary E Peterson, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville; Michael J Chambers, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville; Sarah Andrews, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville; Jinghua Lu, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville; Joshua Tan, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville; Shanping Li, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville; Safiatou Doumbo, University of Sciences, Technique and Technology of Bamako; Kassoum Kayentao, University of Sciences, Technique and Technology of Bamako; Aissata Ongoiba, University of Sciences, Technique and Technology of Bamako; Boubacar Traore, University of Sciences, Technique and Technology of Bamako; Silvia Portugal, Max Planck Institute for Infection Biology,; Peter D Sun, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville; Carole Long, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville; Richard A Koup, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville; Eric O Long, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville; Adrian B McDermott, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville; Peter D Crompton, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville
• Journal Title: JOURNAL OF EXPERIMENTAL MEDICINE
• Volume: Volume 218, Number 4
• Publisher: ROCKEFELLER UNIV PRESS | 2021-04-05
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1084/jem.20200901
• Subjects: Health Sciences, Immunology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Immunology; Medicine, Research & Experimental; Research & Experimental Medicine; HUMAN MONOCLONAL-ANTIBODIES; ACQUIRED-IMMUNITY; BLOOD; SURFACE; INFECTION; GENERATION; EXPRESSION; RESPONSES; ANTIGENS; REVEALS

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-specificMBCs 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.