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Dengue Virus Directly Stimulates Polyclonal B Cell Activation.

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Dengue virus (DENV) directly activates human B cells, inducing IgM secretion and inflammatory markers. This B cell activation occurs independently of prior dengue immunity, suggesting a role in severe dengue pathogenesis.

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Area of Science:

  • Immunology
  • Virology
  • Cell Biology

Background:

  • Dengue infection triggers significant inflammation and B cell activation.
  • Cross-reactive antibodies are elevated in dengue patients.
  • The direct impact of dengue virus on B cells is not fully understood.

Purpose of the Study:

  • To investigate if direct dengue virus (DENV) infection activates primary human B cells.
  • To explore the mechanisms and consequences of DENV-induced B cell activation.

Main Methods:

  • Primary human B lymphocytes were cultured with DENV in vitro.
  • B cell activation markers, cytokine secretion (IgM, IL-6), and signaling pathways (MAPK, CD81) were analyzed.
  • Comparisons were made between DENV-naïve and DENV-immune donors, and between isolated B cells and PBMCs.

Main Results:

  • B cells were susceptible but poorly permissive to DENV infection.
  • DENV induced significant IgM secretion, indicating polyclonal B cell activation.
  • Activation occurred in both DENV-naïve and DENV-immune B cells, dependent on MAPK and CD81.
  • DENV-cultured B cells showed increased IL-6, CD86, and HLA-DR expression.
  • IgG secretion was observed in PBMCs but not isolated B cells, suggesting T cell involvement.

Conclusions:

  • DENV directly activates human B cells, leading to IgM production and inflammatory marker upregulation.
  • This activation is independent of pre-existing dengue immunity and involves specific signaling pathways.
  • DENV-induced B cell activation may contribute to the heightened inflammatory response in severe dengue.
  • In vivo interactions with other immune cells likely promote B cell class switching and IgG production.