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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5 April 2021
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March 04 2021
Plasmodium falciparum–specific IgM B cells dominate in children, expand with malaria, and produce functional IgM
Christine S. Hopp
,
Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing
1
Malaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD
Correspondence to Christine S. Hopp: christine.hopp@nih.gov
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Padmapriya Sekar
,
Padmapriya Sekar
Investigation, Methodology, Resources, Writing - review & editing
2
Molecular and Cellular Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD
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Ababacar Diouf
,
Ababacar Diouf
Investigation
3
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD
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Kazutoyo Miura
,
Kazutoyo Miura
Data curation, Formal analysis, Investigation, Visualization, Writing - review & editing
3
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD
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Kristin Boswell
,
Kristin Boswell
Investigation
4
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
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Jeff Skinner
,
Jeff Skinner
Data curation, Formal analysis
1
Malaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD
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Christopher M. Tipton
,
Christopher M. Tipton
Formal analysis
5
Lowance Center for Human Immunology, Division of Rheumatology, Department of Medicine, Emory University School of Medicine, Atlanta, GA
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Mary E. Peterson
,
Mary E. Peterson
Investigation
1
Malaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD
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Michael J. Chambers
,
Michael J. Chambers
Methodology
4
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
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Sarah Andrews
,
Sarah Andrews
Methodology, Resources, Writing - review & editing
4
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
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Jinghua Lu
,
Jinghua Lu
Investigation
6
Structural Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD
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Joshua Tan
,
Joshua Tan
Investigation, Methodology, Resources, Validation
7
Antibody Biology Unit, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD
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Shanping Li
,
Shanping Li
Investigation
1
Malaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD
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Safiatou Doumbo
,
Safiatou Doumbo
Conceptualization, Data curation, Investigation, Validation, Writing - original draft, Writing - review & editing
8
Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, Bamako, Mali
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Kassoum Kayentao
,
Kassoum Kayentao
Investigation, Supervision, Writing - review & editing
8
Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, Bamako, Mali
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Aissata Ongoiba
,
Aissata Ongoiba
Investigation, Project administration
8
Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, Bamako, Mali
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Boubacar Traore
,
Boubacar Traore
Data curation, Investigation, Project administration, Resources, Validation
8
Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, Bamako, Mali
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Silvia Portugal
,
Silvia Portugal
Investigation
9
Max Planck Institute for Infection Biology, Berlin, Germany
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Peter D. Sun
,
Peter D. Sun
Data curation, Methodology
6
Structural Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD
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Carole Long
,
Carole Long
Data curation, Investigation, Validation
3
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD
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Richard A. Koup
,
Richard A. Koup
Formal analysis, Methodology, Supervision, Writing - review & editing
4
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
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Eric O. Long
,
Eric O. Long
Funding acquisition, Supervision, Writing - review & editing
2
Molecular and Cellular Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD
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Adrian B. McDermott
,
Adrian B. McDermott
Conceptualization, Methodology, Supervision
4
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
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Peter D. Crompton
Conceptualization, Funding acquisition, Project administration, Resources, Supervision, Writing - review & editing
1
Malaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD
Peter D. Crompton: pcrompton@niaid.nih.gov
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Christine S. Hopp
Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing
1
Malaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD
Padmapriya Sekar
Investigation, Methodology, Resources, Writing - review & editing
2
Molecular and Cellular Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD
Ababacar Diouf
Investigation
3
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD
Kazutoyo Miura
Data curation, Formal analysis, Investigation, Visualization, Writing - review & editing
3
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD
Kristin Boswell
Investigation
4
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
Jeff Skinner
Data curation, Formal analysis
1
Malaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD
Christopher M. Tipton
Formal analysis
5
Lowance Center for Human Immunology, Division of Rheumatology, Department of Medicine, Emory University School of Medicine, Atlanta, GA
Mary E. Peterson
Investigation
1
Malaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD
Michael J. Chambers
Methodology
4
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
Sarah Andrews
Methodology, Resources, Writing - review & editing
4
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
Jinghua Lu
Investigation
6
Structural Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD
Joshua Tan
Investigation, Methodology, Resources, Validation
7
Antibody Biology Unit, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD
Shanping Li
Investigation
1
Malaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD
Safiatou Doumbo
Conceptualization, Data curation, Investigation, Validation, Writing - original draft, Writing - review & editing
8
Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, Bamako, Mali
Kassoum Kayentao
Investigation, Supervision, Writing - review & editing
8
Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, Bamako, Mali
Aissata Ongoiba
Investigation, Project administration
8
Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, Bamako, Mali
Boubacar Traore
Data curation, Investigation, Project administration, Resources, Validation
8
Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, Bamako, Mali
Silvia Portugal
Investigation
9
Max Planck Institute for Infection Biology, Berlin, Germany
Peter D. Sun
Data curation, Methodology
6
Structural Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD
Carole Long
Data curation, Investigation, Validation
3
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD
Richard A. Koup
Formal analysis, Methodology, Supervision, Writing - review & editing
4
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
Eric O. Long
Funding acquisition, Supervision, Writing - review & editing
2
Molecular and Cellular Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD
Adrian B. McDermott
Conceptualization, Methodology, Supervision
4
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
Peter D. Crompton
Conceptualization, Funding acquisition, Project administration, Resources, Supervision, Writing - review & editing
1
Malaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD
Correspondence to Christine S. Hopp: christine.hopp@nih.gov
Peter D. Crompton: pcrompton@niaid.nih.gov
Disclosures: The authors declare no competing interests exist.
Received:
May 05 2020
Revision Received:
November 21 2020
Accepted:
January 21 2021
Online Issn: 1540-9538
Print Issn: 0022-1007
Funding:
Division of Intramural Research, National Institute of Allergy and Infectious Diseases
(NO AWARD)
National Institutes of Health
(NO AWARD)
© 2021 Hopp et al.
2021
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
J Exp Med (2021) 218 (4): e20200901.
Article history
Received:
May 05 2020
Revision Received:
November 21 2020
Accepted:
January 21 2021
Citation
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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