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

PLoS Pathogens

Edward A. Clark¹  Christiane Dresch²  Daniela Giordano²  Kevin E. Draves²  Lucy B. Young²  Marianne A. Bryan²  Kelsey Roe²  Michael S. Diamond³  Justin M. Richner³  Michael Gale Jr⁴ 

[1] Center for Innate Immunity and Immune Disease, University of Washington, Seattle, Washington, United States of America;Department of Immunology, University of Washington, Seattle, Washington, United States of America;Departments of Medicine, Molecular Microbiology, Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri, United States of America;The Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St Louis, Missouri, United States of America

关键词: West Nile virus;    B cells;    T cells;    Cytotoxic T cells;    Immune serum;    Immune response;    Enzyme-linked immunoassays;    Cell-mediated immunity;   

DOI  :  10.1371/journal.ppat.1006743

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY