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

Autor: Daniela Giordano, Kevin E Draves, Lucy B Young, Kelsey Roe, Marianne A Bryan, Christiane Dresch, Justin M Richner, Michael S Diamond, Michael Gale, Edward A Clark
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: PLoS Pathogens, Vol 13, Iss 11, p e1006743 (2017)
Druh dokumentu: article
ISSN: 1553-7366
1553-7374
DOI: 10.1371/journal.ppat.1006743
Popis: 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.
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