The regulation of inherently autoreactive VH4-34-expressing B cells in individuals living in a malaria-endemic area of West Africa

Geoffrey T. Hart, Munir Akkaya, Asiya S. Chida, Chungwen Wei, Scott A. Jenks, Christopher Tipton, Chenfeng He, Ben S. Wendel, Jeff Skinner, Gunjan Arora, Kassoum Kayentao, Aissata Ongoiba, Ogobara Doumbo, Boubacar Traore, David L. Narum, Ning Jiang, Peter D. Crompton, Ignacio Sanz, Susan K. Pierce

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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.

Original languageEnglish (US)
Pages (from-to)3841-3849
Number of pages9
JournalJournal of Immunology
Volume197
Issue number10
DOIs
StatePublished - Nov 15 2016

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Western Africa
Malaria
B-Lymphocytes
Immunoglobulin G
Falciparum Malaria
Communicable Diseases
Adaptive Immunity
Acute Disease
Humoral Immunity
Fever
Phenotype
Infection

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The regulation of inherently autoreactive VH4-34-expressing B cells in individuals living in a malaria-endemic area of West Africa. / Hart, Geoffrey T.; Akkaya, Munir; Chida, Asiya S.; Wei, Chungwen; Jenks, Scott A.; Tipton, Christopher; He, Chenfeng; Wendel, Ben S.; Skinner, Jeff; Arora, Gunjan; Kayentao, Kassoum; Ongoiba, Aissata; Doumbo, Ogobara; Traore, Boubacar; Narum, David L.; Jiang, Ning; Crompton, Peter D.; Sanz, Ignacio; Pierce, Susan K.

In: Journal of Immunology, Vol. 197, No. 10, 15.11.2016, p. 3841-3849.

Research output: Contribution to journalArticle

Hart, GT, Akkaya, M, Chida, AS, Wei, C, Jenks, SA, Tipton, C, He, C, Wendel, BS, Skinner, J, Arora, G, Kayentao, K, Ongoiba, A, Doumbo, O, Traore, B, Narum, DL, Jiang, N, Crompton, PD, Sanz, I & Pierce, SK 2016, 'The regulation of inherently autoreactive VH4-34-expressing B cells in individuals living in a malaria-endemic area of West Africa', Journal of Immunology, vol. 197, no. 10, pp. 3841-3849. https://doi.org/10.4049/jimmunol.1600491
Hart, Geoffrey T. ; Akkaya, Munir ; Chida, Asiya S. ; Wei, Chungwen ; Jenks, Scott A. ; Tipton, Christopher ; He, Chenfeng ; Wendel, Ben S. ; Skinner, Jeff ; Arora, Gunjan ; Kayentao, Kassoum ; Ongoiba, Aissata ; Doumbo, Ogobara ; Traore, Boubacar ; Narum, David L. ; Jiang, Ning ; Crompton, Peter D. ; Sanz, Ignacio ; Pierce, Susan K. / The regulation of inherently autoreactive VH4-34-expressing B cells in individuals living in a malaria-endemic area of West Africa. In: Journal of Immunology. 2016 ; Vol. 197, No. 10. pp. 3841-3849.
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AU - Jenks, Scott A.

AU - Tipton, Christopher

AU - He, Chenfeng

AU - Wendel, Ben S.

AU - Skinner, Jeff

AU - Arora, Gunjan

AU - Kayentao, Kassoum

AU - Ongoiba, Aissata

AU - Doumbo, Ogobara

AU - Traore, Boubacar

AU - Narum, David L.

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AU - Pierce, Susan K.

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