Towards understanding the expansion of plasmablasts in dengue virus infections (HEM4P.254)

Abstract

Abstract An increased prevalence of dengue has resulted in its emergence as an important public health threat. Pre-immunity to any of the 4 dengue virus (DENV) serotypes is the main risk factor for developing severe disease during heterologous DENV infections. We have recently published that during secondary DENV infections there is a major expansion of DENV-specific antibody secreting plasmablasts (CD19+CD27+CD38+) that correlates with the development of severe disease. The mechanisms driving this response remain unknown and may be important in understanding the pathogenesis of DENV infections. We are using in vitro approaches to define the possible mechanisms responsible for driving expansion of plasmablasts during heterologous DENV exposures. PBMCs from a cohort of healthy DENV seropositive and seronegative donors were collected for this study. We used flow cytometry to assess the differentiation of B-cells into plasmablasts 7 days after stimulating PBMCs with each DENV serotype. Preliminary in vitro studies suggest that B-cells from DENV immune donors are more apt to differentiate into plasmablasts when stimulated with DENV with possible variances between the different serotypes. Our results with isolated B-cells also suggest that the presence of other cell populations, potentially monocytes, is required for the expansion of plasmablasts. Ongoing experiments will reveal further cellular requirements for the in vitro expansion of plasmablasts after exposure to heterologous DENV.