Dynamics of Dengue Virus (DENV)-Specific B Cells in the Response to DENV Serotype 1 Infections, Using Flow Cytometry With Labeled Virions

• Published in: The Journal of infectious diseases Vol. 214; no. 7; pp. 1001 - 1009
• Main Authors: Woda, Marcia, Friberg, Heather, Currier, Jeffrey R., Srikiatkhachorn, Anon, Macareo, Louis R., Green, Sharone, Jarman, Richard G., Rothman, Alan L., Mathew, Anuja
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.10.2016
• Subjects: Adolescent; B-Lymphocytes - immunology; Child; Child, Preschool; Dengue - immunology; Dengue - virology; Dengue Virus - immunology; Female; Flaviviridae; Flow Cytometry; Humans; Immunoassay - methods; Infant; Major and Brief Reports; Male; Serogroup; Staining and Labeling - methods; Thailand; Virion - immunology; VIRUSES; ISEW, Thailand; B cell; flow cytometry; Alexa Fluor; antigen; Dengue
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiw308

Background. The development of reagents to identify and characterize antigen-specific B cells has been challenging. Methods. We recently developed Alexa Fluor-labeled dengue viruses (AF DENVs) to characterize antigen-specific B cells in the peripheral blood of DENV-immune individuals. Results. In this study, we used AF DENV serotype 1 (AF DENV-1) together with AF DENV-2 on peripheral blood mononuclear cells (PBMCs) from children in Thailand with acute primary or secondary DENV-1 infections to analyze the phenotypes of antigenspecific cells that reflected their exposure or clinical diagnosis. DENV serotype-specific and cross-reactive B cells were identified in PBMCs from all subjects. Frequencies of AF DENV⁺ class-switched memory B cells (IgD⁻CD27⁺ CD19⁺ cells) reached up to 8% during acute infection and early convalescence. AF DENV-labeled B cells expressed high levels of CD27 and CD38 during acute infection, characteristic of plasmablasts, and transitioned into memory cells (CD38⁻CD27⁺) at the early convalescent time point. There was higher activation of memory cells early during acute secondary infection, suggesting reactivation from a previous DENV infection. Conclusions. AF DENVs reveal changes in the phenotype of DENV serotype-specific and cross-reactive cells during and after natural DENV infection and could be useful in analysis of the response to DENV vaccination.