Immunity to viruses in B cell-deficient mice: influence of antibodies on virus persistence and T cell memory
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Mice rendered B cell deficient by targeted disruption of the immunoglobulin p chain gene (IgM-/-mice) were used to analyze the role of antibodies and B cells in viral infections; homozygous IgM-/-mice were bred in a way to avoid transmission of maternal antibodies. After infection with vesicular stomatitis virus (VSV), IgM-/-mice developed paralytic disease and subsequently died, whereas C57BW6 control mice or IgM-/-mice passively protected with VSVneutralizing antibodies survived. Furthermore, IgM-/-mice showed increased natural killer (NK) activity upon exposure to either lymphocytic choriomeningitis virus (LCMV) or to poly(1) . poly(C), while NK activity in untreated IgM-/-mice was within normal ranges. Cytotoxic T cell responses were comparable in IgM-/-and control mice infected either with VSV or with vaccinia virus or with low doses of LCMV (lo2 infectious focus-forming units [ifu]). After intracerebral infection with LCMV-Armstrong, CD8' T cell-mediated lethal lymphocytic choriomeningitis developed independently of the presence of B cells and antibodies. After infection with high doses (2 X 10' -5 X 10' ifu) of LCMV-WE or LCMV-Docile, IgM-/-mice exhibited a reduced capacity to control these primary infections and had elevated virus titers for prolonged times (> 60 days). Nevertheless, the cytotoxic T cell response against LCMV in the early phase of infection was comparable in IgM-/-and control mice, but disappeared in those IgM-/-mice which had a persistent viral infection. Cytotoxic T cell memory was apparently unimpaired in low-dose-primed IgM-/mice, which were able to control the primary virus infection; both IgM-/-and control mice cleared a high intravenous dose of virus within 2 days after challenge infection. This indicates that an efficient T cell memory against LCMV was established in the absence of B cells.