title: B-cell responses during primary and secondary dengue virus infections in humans.
abstract: Low-avidity serotype-cross-reactive antibodies are hypothesized to play a key role in triggering severe disease in patients with secondary dengue virus (DENV) infection. However, there is little systematic information about the frequency, avidity, and cross-reactivity of DENV-specific B cells in individuals experiencing primary instead of secondary infection. We compared DENV-specific B-cell responses in a cohort of Thai children with primary or secondary DENV infection. B cells specific for DENV precursor membrane protein, envelope (E) protein, and nonstructural protein 1 were detectable in immune peripheral blood mononuclear cells with the highest frequencies of DENV E-specific B cells detected in patients experiencing primary DENV-1 infections. DENV E-specific B cells were highly serotype-specific after primary DENV infections, whereas most E-specific B cells in patients with secondary infection were serotype-cross-reactive and secreted antibodies with higher avidity to heterologous DENV serotypes. Our data suggest that the minor populations of serotype-cross-reactive B cells generated by primary DENV infection are preferentially expanded during secondary DENV infection.
authors.affiliation: Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA. anuja.mathew@umassmed.edu
authors.forename: Anuja
authors.initials: A
authors.lastname: Mathew
authors.forename: Kim
authors.initials: K
authors.lastname: West
authors.forename: Siripen
authors.initials: S
authors.lastname: Kalayanarooj
authors.forename: Robert V
authors.initials: RV
authors.lastname: Gibbons
authors.forename: Anon
authors.initials: A
authors.lastname: Srikiatkhachorn
authors.forename: Sharone
authors.initials: S
authors.lastname: Green
authors.forename: Daniel
authors.initials: D
authors.lastname: Libraty
authors.forename: Smita
authors.initials: S
authors.lastname: Jaiswal
authors.forename: Alan L
authors.initials: AL
authors.lastname: Rothman
mesh_terms: D000293:Adolescent; D000914:Antibodies, Viral / Q000097:blood* / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003429:Cross Reactions; D003715:Dengue / Q000276:immunology*; D003716:Dengue Virus / Q000145:classification / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007223:Infant; D012703:Serotyping; D013785:Thailand; D014759:Viral Envelope Proteins / Q000276:immunology / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; C079340:NS1 protein, Dengue virus type 2; D014759:Viral Envelope Proteins; D017361:Viral Nonstructural Proteins