Marcia Woda1, Heather Friberg2, Jeffrey R Currier2, Anon Srikiatkhachorn3, Louis R Macareo4, Sharone Green5, Richard G Jarman2, Alan L Rothman6, Anuja Mathew1. 1. Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester Institute for Immunology and Informatics, University of Rhode Island, Providence. 2. Walter Reed Army Institute of Research, Silver Spring, Maryland. 3. Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand. 4. Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand. 5. Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester. 6. Institute for Immunology and Informatics, University of Rhode Island, Providence.
Abstract
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 antigen-specific B 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 B cells (CD38(-)CD27(+)) at the early convalescent time point. There was higher activation of memory B 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 B cells during and after natural DENV infection and could be useful in analysis of the response to DENV vaccination.
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 AFDENV serotype 1 (AFDENV-1) together with AFDENV-2 on peripheral blood mononuclear cells (PBMCs) from children in Thailand with acute primary or secondary DENV-1 infections to analyze the phenotypes of antigen-specific B 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 AFDENV(+) class-switched memory B cells (IgD(-)CD27(+) CD19(+) cells) reached up to 8% during acute infection and early convalescence. AFDENV-labeled B cells expressed high levels of CD27 and CD38 during acute infection, characteristic of plasmablasts, and transitioned into memory B cells (CD38(-)CD27(+)) at the early convalescent time point. There was higher activation of memory B cells early during acute secondary infection, suggesting reactivation from a previous DENVinfection. CONCLUSIONS:AF DENVs reveal changes in the phenotype of DENV serotype-specific and cross-reactive B cells during and after natural DENVinfection and could be useful in analysis of the response to DENV vaccination.
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