title: Association between magnitude of the virus-specific plasmablast response and disease severity in dengue patients.
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.
authors.affiliation: Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Tatiana M
authors.initials: TM
authors.lastname: Garcia-Bates
authors.forename: Marli T
authors.initials: MT
authors.lastname: Cordeiro
authors.forename: Eduardo J M
authors.initials: EJ
authors.lastname: Nascimento
authors.forename: Amanda P
authors.initials: AP
authors.lastname: Smith
authors.forename: Klécia M
authors.initials: KM
authors.lastname: Soares de Melo
authors.forename: Sean P
authors.initials: SP
authors.lastname: McBurney
authors.forename: Jared D
authors.initials: JD
authors.lastname: Evans
authors.forename: Ernesto T A
authors.initials: ET
authors.lastname: Marques
authors.forename: Simon M
authors.initials: SM
authors.lastname: Barratt-Boyes
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology / Q000821:virology; D001938:Brazil; D002648:Child; D015331:Cohort Studies; D003715:Dengue / Q000276:immunology / Q000473:pathology* / Q000821:virology*; D003716:Dengue Virus / Q000276:immunology* / Q000472:pathogenicity; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010950:Plasma Cells / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D012720:Severity of Illness Index; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology / Q000821:virology; D055815:Young Adult