NIAID-DVI: B-cell responses to dengue infection -- Jens Wrammert

Blog Series: NIAID-DVI

Human B cell responses during dengue infection
Jens Wrammert
Emory University

"Humoral immune responses are thought to play a major role in dengue-induced immuno-pathology, however little is known about the plasmablasts producing these antibodies during an ongoing infection." ~Jens

•  The group analyzed plasmablast responses in patients with acute dengue infection.
• plasmablast responses increased more than 1000 fold over baseline levels.
• These responses made up as much as 30% of the peripheral lymphocyte population
• Responses were dengue specific
• IgG secreting cells that reached high numbers after fever onset coinciding with 'the window' where serious dengue-induced pathology is observed.

Jens' recent paper: Rapid and massive virus-specific plasmablast responses during acute dengue virus infection in humans. 2012. JVI 86: 2911.

 

What is a plasmablast?

"The most immature blood cell that is considered a plasma cell instead of a B cell is the plasmablast. Plasmablasts secrete more antibodies than B cells, but less than plasma cells. They divide rapidly and are still capable of internalizing antigens and presenting them to T cells. A cell may stay in this state for several days, and then either die or irrevocably differentiate into a mature, fully differentiated plasma cell." ~Wikipedia

"A plasmablast is basically a B cell that is actively secreting antibodies. This is in response to acute infection only so it is not 'long term' "~Dr. Friberg-Robertson, Immunologist and Friend Extraordinaire 

Questions raised:

Do these cells have a role in dengue immuno-pathology during an ongoing infection?

Ongoing/Future Research to answer said question:

• Understanding the complete repertoire and specificity of the antibodies that are secreted [en masse] by the plasmablasts.
• Jens' group has/is generated panels of human monoclonal antibodies from dengue infection-induced plasmablasts for 5 patients and have done initial functional analyses...stay tuned into his research for the results.

Other papers that highlight plasmablast responses in dengue infection:

• Simmons et al., 2007. Patterns of host genome--wide gene transcript abundance in the peripheral blood of patients with acute dengue hemorrhagic fever. JID 195: 1097.
• Xu et al., 2012. Plasmablasts generated during repeated dengue infection are virus glycoprotein-specific and bind to multiple virus serotypes. J Immunol 189: 5877.
• Garcia-Bates et al., 2012. Association between magnitude of the virus-specific plasmablast response and disease severity in dengue patients. J Immunol 190: 80.