title: The V gene repertoires of classical and atypical memory B cells in malaria-susceptible West African children.
abstract: Immunity to Plasmodium falciparum malaria is naturally acquired in individuals living in malaria-endemic areas of Africa. Abs play a key role in mediating this immunity; however, the acquisition of the components of Ab immunity, long-lived plasma cells and memory B cells (MBCs), is remarkably inefficient, requiring years of malaria exposure. Although long-lived classical MBCs (CD19(+)/CD20(+)/CD21(+)/CD27(+)/CD10(-)) are gradually acquired in response to natural infection, exposure to P. falciparum also results in a large expansion of what we have termed atypical MBCs (CD19(+)/CD20(+)/CD21(-)/CD27(-)/CD10(-)). At present, the function of atypical MBCs in malaria is not known, nor are the factors that drive their differentiation. To gain insight into the relationship between classical and atypical IgG(+) MBCs, we compared the Ab H and L chain V gene repertoires of children living in a malaria-endemic region in Mali. We found that these repertoires were remarkably similar by a variety of criteria, including V gene usage, rate of somatic hypermutation, and CDR-H3 length and composition. The similarity in these repertoires suggests that classical MBCs and atypical MBCs differentiate in response to similar Ag-dependent selective pressures in malaria-exposed children and that atypical MBCs do not express a unique V gene repertoire.
authors.affiliation: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852; severin.zinocker@gmail.com spierce@nih.gov.
authors.forename: Severin
authors.identifier: http://orcid.org/0000-0003-1730-0125
authors.initials: S
authors.lastname: Zinöcker
authors.affiliation: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852;
authors.forename: Christine E
authors.initials: CE
authors.lastname: Schindler
authors.affiliation: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852;
authors.forename: Jeff
authors.initials: J
authors.lastname: Skinner
authors.affiliation: Laboratory for Neonatology and Pediatric Immunology, Department of Pediatrics, Philipps-University, D-35032 Marburg, Germany;
authors.forename: Tobias
authors.initials: T
authors.lastname: Rogosch
authors.affiliation: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852; Department of Pathology, University of Virginia School of Medicine, Charlottesville, VA 22908;
authors.forename: Michael
authors.initials: M
authors.lastname: Waisberg
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510; and.
authors.forename: Jean-Nicolas
authors.initials: JN
authors.lastname: Schickel
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510; and.
authors.forename: Eric
authors.initials: E
authors.lastname: Meffre
authors.affiliation: Mali International Center for Excellence in Research, University of Sciences, Technique and Technology of Bamako, Bamako, Mali.
authors.forename: Kassoum
authors.initials: K
authors.lastname: Kayentao
authors.affiliation: Mali International Center for Excellence in Research, University of Sciences, Technique and Technology of Bamako, Bamako, Mali.
authors.forename: Aïssata
authors.initials: A
authors.lastname: Ongoïba
authors.affiliation: Mali International Center for Excellence in Research, University of Sciences, Technique and Technology of Bamako, Bamako, Mali.
authors.forename: Boubacar
authors.initials: B
authors.lastname: Traoré
authors.affiliation: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852; severin.zinocker@gmail.com spierce@nih.gov.
authors.forename: Susan K
authors.initials: SK
authors.lastname: Pierce
mesh_terms: D000354:Africa, Western; D000595:Amino Acid Sequence; D000953:Antigens, Protozoan / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D022801:Complementarity Determining Regions / Q000235:genetics; D004198:Disease Susceptibility; D005260:Female; D015322:Gene Rearrangement, B-Lymphocyte; D014644:Genetic Variation; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000737:chemistry / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000737:chemistry / Q000235:genetics*; D007156:Immunologic Memory / Q000235:genetics*; D016130:Immunophenotyping; D008288:Malaria / Q000235:genetics* / Q000276:immunology*; D016778:Malaria, Falciparum / Q000235:genetics / Q000276:immunology; D008297:Male; D010963:Plasmodium falciparum / Q000276:immunology; D027041:Somatic Hypermutation, Immunoglobulin
chemical_list: D000953:Antigens, Protozoan; D022801:Complementarity Determining Regions; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region