Association between magnitude of the virus-specific plasmablast response and disease severity in dengue patients

Tatiana M. Garcia-Bates, Marli T. Cordeiro, Eduardo J.M. Nascimento, Amanda P. Smith, Kléia M.Soares De Melo, Sean P. McBurney, Jared D. Evans, Ernesto T.A. Marques, Simon M. Barratt-Boyes

Research output: Contribution to journalArticlepeer-review

Abstract

Dengue is a globally expanding disease caused by infection with dengue virus (DENV) that ranges from febrile illness to acute disease with serious complications. Secondary infection predisposes individuals to more severe disease, and B lymphocytes may play a role in this phenomenon through production of Ab that enhance infection. To better define the acute B cell response during dengue, we analyzed peripheral B cells from an adult Brazilian hospital cohort with primary and secondary DENV infections of varying clinical severity. Circulating B cells in dengue patients were proliferating, activated, and apoptotic relative to individuals with other febrile illnesses. Severe secondary DENV infection was associated with extraordinary peak plasmablast frequencies between 4 and 7 d of illness, averaging 46% and reaching 87% of B cells, significantly greater than those seen in mild illness or primary infections. On average >70% of IgG-secreting cells in individuals with severe secondary DENV infection were DENV specific. Plasmablasts produced Ab that cross-reacted with heterotypic DENV serotypes, but with a 3-fold greater reactivity to DENV-3, the infecting serotype. Plasmablast frequency did not correlate with acute serum-neutralizing Ab titers to any DENV serotype regardless of severity of disease. These findings indicate that massive expansion of DENV-specific and serotype cross-reactive plasmablasts occurs in acute secondary DENV infection of adults in Brazil, which is associated with increasing disease severity.

Original languageEnglish (US)
Pages (from-to)80-87
Number of pages8
JournalJournal of Immunology
Volume190
Issue number1
DOIs
StatePublished - Jan 1 2013

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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