title: Dengue Virus Directly Stimulates Polyclonal B Cell Activation.
abstract: Dengue infection is associated to vigorous inflammatory response, to a high frequency of activated B cells, and to increased levels of circulating cross-reactive antibodies. We investigated whether direct infection of B cells would promote activation by culturing primary human B lymphocytes from healthy donors with DENV in vitro. B cells were susceptible, but poorly permissive to infection. Even though, primary B cells cultured with DENV induced substantial IgM secretion, which is a hallmark of polyclonal B cell activation. Notably, DENV induced the activation of B cells obtained from either DENV immune or DENV naïve donors, suggesting that it was not dependent on DENV-specific secondary/memory response. B cell stimulation was dependent on activation of MAPK and CD81. B cells cultured with DENV also secreted IL-6 and presented increased expression of CD86 and HLA-DR, which might contribute to B lymphocyte co-stimulatory function. Indeed, PBMCs, but not isolated B cells, secreted high amounts of IgG upon DENV culture, suggesting that interaction with other cell types in vivo might promote Ig isotype switching and IgG secretion from different B cell clones. These findings suggest that activation signaling pathways triggered by DENV interaction with non-specific receptors on B cells might contribute to the exacerbated response observed in dengue patients.
authors.affiliation: Departamento de Virologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil.
authors.forename: Arturo Ramon Vargas
authors.initials: AR
authors.lastname: Correa
authors.affiliation: Departamento de Virologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil.
authors.forename: Ana Carolina Egypto Rosa
authors.initials: AC
authors.lastname: Berbel
authors.affiliation: Departamento de Virologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil.
authors.forename: Michelle Premazzi
authors.initials: MP
authors.lastname: Papa
authors.affiliation: Departamento de Virologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil.
authors.forename: Ana Theresa Silveira de
authors.initials: AT
authors.lastname: Morais
authors.affiliation: Departamento de Imunologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil.
authors.forename: Ligia Maria Torres
authors.initials: LM
authors.lastname: Peçanha
authors.affiliation: Departamento de Virologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil.
authors.forename: Luciana Barros de
authors.initials: LB
authors.lastname: Arruda
mesh_terms: D000330:Aedes / Q000166:cytology; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D002460:Cell Line; D003715:Dengue / Q000276:immunology* / Q000473:pathology / Q000821:virology; D003716:Dengue Virus / Q000235:genetics / Q000472:pathogenicity*; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008213:Lymphocyte Activation; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010641:Phenotype; D012367:RNA, Viral / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D060225:Tetraspanin 28 / Q000378:metabolism
chemical_list: D000914:Antibodies, Viral; D051940:B7-2 Antigen; D006684:HLA-DR Antigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D015850:Interleukin-6; D012367:RNA, Viral; D060225:Tetraspanin 28; D020928:Mitogen-Activated Protein Kinases