Immunity to viruses in B cell‐deficient mice: Influence of antibodies on virus persistence and on T cell memory

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Abstract
Mice rendered B cell deficient by targeted disruption of the immunoglobulin μ 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 C57BL/6 control mice or IgM−/− mice passively protected with VSV-neutralizing antibodies survived. Furthermore, IgM−/− mice showed increased natural killer (NK) activity upon exposure to either lymphocytic choriomeningitis virus (LCMV) or to poly(I) · 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 (102 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 × 106 − 5 × 106 ifu) of LCMV-WE or LCMV-Docile, IgM−/− mice exhibited a reduced capacity to control these primary infections and had elevated virus liters 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.