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

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

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

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 cell 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-/-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.

Original languageEnglish
Article numbere1006743
JournalPLoS pathogens
Volume13
Issue number11
DOIs
StatePublished - Nov 2017

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    Giordano, D., Draves, K. E., Young, L. B., Roe, K., Bryan, M. A., Dresch, C., Richner, J. M., Diamond, M. S., Gale, M., & Clark, E. A. (2017). Protection of mice deficient in mature B cells from West Nile virus infection by passive and active immunization. PLoS pathogens, 13(11), [e1006743]. https://doi.org/10.1371/journal.ppat.1006743