Dengue Virus Directly Stimulates Polyclonal B Cell Activation

• Published in: PloS one Vol. 10; no. 12; p. e0143391
• Main Authors: Correa, Arturo Ramon Vargas, Berbel, Ana Carolina Egypto Rosa, Papa, Michelle Premazzi, Morais, Ana Theresa Silveira de, Peçanha, Ligia Maria Torres, Arruda, Luciana Barros de
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10-12-2015; Public Library of Science (PLoS)
• Subjects: Aedes - cytology; Animals; Antibodies; Antibodies, Viral - analysis; B cells; B-Lymphocytes - cytology; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; B7-2 Antigen - metabolism; CD81 antigen; CD86 antigen; Cell activation; Cell culture; Cell growth; Cell Line; Class switching; Dengue; Dengue - immunology; Dengue - pathology; Dengue - virology; Dengue fever; Dengue virus; Dengue Virus - genetics; Dengue Virus - pathogenicity; Health aspects; Hepatitis; Histocompatibility antigen HLA; HLA-DR Antigens - metabolism; Humans; Immunoglobulin G; Immunoglobulin G - metabolism; Immunoglobulin M; Immunoglobulin M - metabolism; Immunoglobulins; Immunological memory; Infection; Infections; Inflammation; Inflammatory response; Interleukin 6; Interleukin-6 - metabolism; Kinases; Lymphocyte Activation; Lymphocytes; Lymphocytes B; MAP kinase; Mitogen-Activated Protein Kinases - metabolism; Phenotype; Real-Time Polymerase Chain Reaction; Receptors; RNA, Viral - analysis; Signal Transduction; Signaling; T cell receptors; Tetraspanin 28 - metabolism; Vector-borne diseases; Viral diseases; Viruses; Brazil; Rio de Janeiro Brazil
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0143391

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.