title: The Regulation of Inherently Autoreactive VH4-34-Expressing B Cells in Individuals Living in a Malaria-Endemic Area of West Africa.
abstract: Plasmodium falciparum malaria is a deadly infectious disease in which Abs play a critical role in naturally acquired immunity. However, the specificity and nature of Abs elicited in response to malaria are only partially understood. Autoreactivity and polyreactivity are common features of Ab responses in several infections and were suggested to contribute to effective pathogen-specific Ab responses. In this article, we report on the regulation of B cells expressing the inherently autoreactive VH4-34 H chain (identified by the 9G4 mAb) and 9G4+plasma IgG in adults and children living in a P. falciparum malaria-endemic area in West Africa. The frequency of 9G4+peripheral blood CD19+B cells was similar in United States adults and African adults and children; however, more 9G4+B cells appeared in classical and atypical memory B cell compartments in African children and adults compared with United States adults. The levels of 9G4+IgG increased following acute febrile malaria but did not increase with age as humoral immunity is acquired or correlate with protection from acute disease. This was the case, even though a portion of 9G4+B cells acquired phenotypes of atypical and classical memory B cells and 9G4+IgG contained equivalent numbers of somatic hypermutations compared with all other VHs, a characteristic of secondary Ab repertoire diversification in response to Ag stimulation. Determining the origin and function of 9G4+B cells and 9G4+IgG in malaria may contribute to a better understanding of the varied roles of autoreactivity in infectious diseases.
authors: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852.
authors: Geoffrey T
authors: GT
authors: Hart
authors: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852.
authors: Munir
authors: 0000-0002-9949-9424
authors: M
authors: Akkaya
authors: Division of Rheumatology, Department of Medicine, Lowance Center for Human Immunology, Emory University, Atlanta, GA 30322.
authors: Asiya S
authors: AS
authors: Chida
authors: Division of Rheumatology, Department of Medicine, Lowance Center for Human Immunology, Emory University, Atlanta, GA 30322.
authors: Chungwen
authors: C
authors: Wei
authors: Division of Rheumatology, Department of Medicine, Lowance Center for Human Immunology, Emory University, Atlanta, GA 30322.
authors: Scott A
authors: SA
authors: Jenks
authors: Adaptive Biotechnologies Seattle, Seattle, WA 98102.
authors: Christopher
authors: C
authors: Tipton
authors: Department of Biomedical Engineering, Cockrell School of Engineering, University of Texas at Austin, Austin, TX 78712.
authors: Chenfeng
authors: 0000-0002-9171-3879
authors: C
authors: He
authors: McKetta Department of Chemical Engineering, Cockrell School of Engineering, University of Texas at Austin, Austin, TX 78712.
authors: Ben S
authors: 0000-0001-6896-3354
authors: BS
authors: Wendel
authors: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852.
authors: Jeff
authors: J
authors: Skinner
authors: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852.
authors: Gunjan
authors: G
authors: Arora
authors: 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; and.
authors: Kassoum
authors: K
authors: Kayentao
authors: 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; and.
authors: Aissata
authors: A
authors: Ongoiba
authors: 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; and.
authors: Ogobara
authors: O
authors: Doumbo
authors: 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; and.
authors: Boubacar
authors: B
authors: Traore
authors: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852.
authors: David L
authors: DL
authors: Narum
authors: Department of Biomedical Engineering, Cockrell School of Engineering, University of Texas at Austin, Austin, TX 78712.
authors: Ning
authors: N
authors: Jiang
authors: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852.
authors: Peter D
authors: PD
authors: Crompton
authors: Division of Rheumatology, Department of Medicine, Lowance Center for Human Immunology, Emory University, Atlanta, GA 30322.
authors: Ignacio
authors: I
authors: Sanz
authors: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852; spierce@nih.gov.
authors: Susan K
authors: 0000-0001-7261-3437
authors: SK
authors: Pierce
mesh_terms: D000328:Adult; D000354:Africa, Western / Q000453:epidemiology; D000913:Antibodies, Protozoan / Q000097:blood* / Q000276:immunology; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D002648:Child; D019353:Endemic Diseases; D005786:Gene Expression Regulation; D006801:Humans; D056724:Immunity, Humoral; D007074:Immunoglobulin G / Q000097:blood* / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology*; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D008288:Malaria / Q000453:epidemiology / Q000276:immunology; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000276:immunology*; D010641:Phenotype; D010963:Plasmodium falciparum / Q000276:immunology; D014481:United States / Q000453:epidemiology
chemical_list: D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M