Protection of mice deficient in mature B cells from West Nile virus infection by passive and active immunization

PLoS Pathog. 2017 Nov 27;13(11):e1006743. doi: 10.1371/journal.ppat.1006743. eCollection 2017 Nov.


B cell activating factor receptor (BAFFR)-/- mice have a profound reduction in mature B cells, but unlike μMT mice, they have normal numbers of newly formed, immature B cells. Using a West Nile virus (WNV) challenge model that requires antibodies (Abs) for protection, we found that unlike wild-type (WT) mice, BAFFR-/- mice were highly susceptible to WNV and succumbed to infection within 8 to 12 days after subcutaneous virus challenge. Although mature B cells were required to protect against lethal infection, infected BAFFR-/- mice had reduced WNV E-specific IgG responses and neutralizing Abs. Passive transfer of immune sera from previously infected WT mice rescued BAFFR-/- and fully B cell-deficient μMT mice, but unlike μMT mice that died around 30 days post-infection, BAFFR-/- mice survived, developed WNV-specific IgG Abs and overcame a second WNV challenge. Remarkably, protective immunity could be induced in mature B cell-deficient mice. Administration of a WNV E-anti-CD180 conjugate vaccine 30 days prior to WNV infection induced Ab responses that protected against lethal infection in BAFFR-/- mice but not in μMT mice. Thus, the immature B cells present in BAFFR-/- and not μMT mice contribute to protective antiviral immunity. A CD180-based vaccine may promote immunity in immunocompromised individuals.

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology*
  • B-Cell Activation Factor Receptor / deficiency
  • B-Cell Activation Factor Receptor / genetics
  • B-Lymphocytes / immunology*
  • Female
  • Humans
  • Immunization, Passive
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Vaccination
  • West Nile Fever / immunology
  • West Nile Fever / prevention & control*
  • West Nile Fever / virology
  • West Nile virus / immunology*
  • West Nile virus / physiology


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • B-Cell Activation Factor Receptor