Rapid and Massive Virus-Specific Plasmablast Responses during Acute Dengue Virus Infection in Humans

• Type of Material: Article
• Authors: Jens Wrammert, Emory University; Nattawat Onlamoon, Mahidol University; Rama Akondy, Emory University; Guey Chuen 'Oscar' Perng, Emory University; Korakot Polsrila, Mahidol University; Anmol Chandele, Emory University; Marcin Kwissa, Emory University; Bali Pulendran, Emory University; Patrick C. Wilson, University of Chicago; Orasri Wittawatmongkol, Mahidol University; Sutee Yoksan, Mahidol University; Nasikarn Angkasekwinai, Mahidol University; Kovit Pattanapanyasat, Mahidol University; Kulkanya Chokephaibulkit, Mahidol University; Rafi Ahmed, Emory University
• Language: English
• Date: 2012-03
• Publisher: American Society for Microbiology
• Publication Version: Final Published Version
• Copyright Statement: © 2012, American Society for Microbiology. All Rights Reserved.
• Final Published Version (URL): http://dx.doi.org/10.1128%2FJVI.06075-11
• Title of Journal or Parent Work: Journal of Virology
• Volume: 86
• Issue: 6
• Start Page: 2911
• End Page: 2918
• Grant/Funding Information: N.O. is supported by a Chalermphrakiat grant from the Faculty of Medicine, Siriraj Hospital, Mahidol University.; K.P. is a Thailand Research Fund Senior Research Scholar.; This work was funded by National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID) grant U19-AI057266 and by the Office of the Higher Education Commission and Mahidol University under the Thai National Research Universities Initiative.
• Research Categories: Biology, Microbiology; Biology, Virology

Abstract

Humoral immune responses are thought to play a major role in dengue virus-induced immunopathology; however, little is known about the plasmablasts producing these antibodies during an ongoing infection. Herein we present an analysis of plasmablast responses in patients with acute dengue virus infection. We found very potent plasmablast responses that often increased more than 1,000-fold over the baseline levels in healthy volunteers. In many patients, these responses made up as much 30% of the peripheral lymphocyte population. These responses were largely dengue virus specific and almost entirely made up of IgG-secreting cells, and plasmablasts reached very high numbers at a time after fever onset that generally coincided with the window where the most serious dengue virus-induced pathology is observed. The presence of these large, rapid, and virus-specific plasmablast responses raises the question as to whether these cells might have a role in dengue immunopathology during the ongoing infection. These findings clearly illustrate the need for a detailed understanding of the repertoire and specificity of the antibodies that these plasmablasts produce.