The Regulation of Inherently Autoreactive VH4-34-Expressing B Cells in Individuals Living in a Malaria-Endemic Area of West Africa

• Type of Material: Article
• Authors: Geoffrey Hart, National Institutes of Health; Munir Akkaya, National Institutes of Health; Asiya Chida, Emory University; Chungwen Wei, Emory University; Scott Jenks, Emory University; Christopher Tipton, Emory University; Chenfeng He, University of Texas Austin; Ben S. Wendel, University of Texas Austin; Jeff Skinner, National Institutes of Health; Gunjan Arora, National Institutes of Health; Kassoum Kayentao, University of Sciences, Technique and Technology of Bamako; Aissata Ongoiba, University of Sciences, Technique and Technology of Bamako; Ogobara Doumbo, University of Sciences, Technique and Technology of Bamako; Boubacar Traore, University of Sciences, Technique and Technology of Bamako; David L. Narum, National Institutes of Health; Ning Jiang, University of Texas Austin; Peter D. Crompton, National Institutes of Health; Ignacio Sanz, Emory University; Susan K. Pierce, National Institutes of Health
• Language: English
• Date: 2016-11-15
• Publisher: American Association of Immunologists
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016 by The American Association of Immunologists, Inc. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.4049/jimmunol.1600491
• Title of Journal or Parent Work: Journal of Immunology
• ISSN: 0022-1767
• Volume: 197
• Issue: 10
• Start Page: 3841
• End Page: 3849
• Grant/Funding Information: his work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health and by grants 5R37AI049660 and U19 AI110483 Autoimmunity Center of Excellence awarded by the National Institutes of Health to I.S.
• Keywords: HIV-1 ANTIBODIES; INFECTION; RESPONSES; 9G4 IDIOTOPE; SYSTEMIC-LUPUS-ERYTHEMATOSUS; NEUTRALIZING ANTIBODIES; GENE SEGMENT; ACQUIRED-IMMUNITY; AUTOIMMUNE-DISEASE; Immunology; PLASMODIUM-FALCIPARUM; Life Sciences & Biomedicine; Science & Technology
• Research Categories: Health Sciences, General; Health Sciences, Immunology

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.