Malaria-associated atypical memory B cells exhibit markedly reduced B cell receptor signaling and effector function
Silvia Portugal,
Christopher M Tipton,
Haewon Sohn,
Younoussou Kone,
Jing Wang,
Shanping Li,
Jeff Skinner,
Kimmo Virtaneva,
Daniel E Sturdevant,
Stephen F Porcella,
Ogobara K Doumbo,
Safiatou Doumbo,
Kassoum Kayentao,
Aissata Ongoiba,
Boubacar Traore,
Inaki Sanz,
Susan K Pierce,
Peter D Crompton
Affiliations
Silvia Portugal
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, United States
Christopher M Tipton
Departments of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, Emory University, Atlanta, United States; Department of Pediatrics, Division of Rheumatology, Lowance Center for Human Immunology, Emory University, Atlanta, United States
Haewon Sohn
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, United States
Younoussou Kone
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
Jing Wang
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, United States
Shanping Li
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, United States
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, United States
Kimmo Virtaneva
Rocky Mountain Laboratory Research Technologies Section, Genomics Unit, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, United States
Daniel E Sturdevant
Rocky Mountain Laboratory Research Technologies Section, Genomics Unit, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, United States
Stephen F Porcella
Rocky Mountain Laboratory Research Technologies Section, Genomics Unit, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, United States
Ogobara K Doumbo
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
Safiatou Doumbo
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
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
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
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
Inaki Sanz
Departments of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, Emory University, Atlanta, United States
Susan K Pierce
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, United States
Peter D Crompton
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, United States
Protective antibodies in Plasmodium falciparum malaria are only acquired after years of repeated infections. Chronic malaria exposure is associated with a large increase in atypical memory B cells (MBCs) that resemble B cells expanded in a variety of persistent viral infections. Understanding the function of atypical MBCs and their relationship to classical MBCs will be critical to developing effective vaccines for malaria and other chronic infections. We show that VH gene repertoires and somatic hypermutation rates of atypical and classical MBCs are indistinguishable indicating a common developmental history. Atypical MBCs express an array of inhibitory receptors and B cell receptor (BCR) signaling is stunted in atypical MBCs resulting in impaired B cell responses including proliferation, cytokine production and antibody secretion. Thus, in response to chronic malaria exposure, atypical MBCs appear to differentiate from classical MBCs becoming refractory to BCR-mediated activation and potentially interfering with the acquisition of malaria immunity.
