Rapid and massive virus-specific plasmablast responses during acute dengue virus infection in humans

人类急性登革热病毒感染期间快速而大量的病毒特异性浆母细胞反应

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作者:Jens Wrammert, Nattawat Onlamoon, Rama S Akondy, Guey C Perng, Korakot Polsrila, Anmol Chandele, Marcin Kwissa, Bali Pulendran, Patrick C Wilson, Orasri Wittawatmongkol, Sutee Yoksan, Nasikarn Angkasekwinai, Kovit Pattanapanyasat, Kulkanya Chokephaibulkit, Rafi Ahmed

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.

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