IMMUNITY TO VIRUSES IN B-CELL-DEFICIENT MICE - INFLUENCE OF ANTIBODIES ON VIRUS PERSISTENCE AND ON T-CELL MEMORY

Mice rendered B cell deficient by targeted disruption of the immunoglo bulin Cc chain gene (IgM-/- mice) were used to analyze the role of ant ibodies and B cells in viral infections; homozygous IgM-/- mice were b red in a way to avoid transmission of maternal antibodies. After infec tion with vesicular stomatitis virus (VSV), IgM-/- mice developed para lytic disease and subsequently died, whereas C57BL/6 control mice or I gM-/- mice passively protected with VSV-neutralizing antibodies surviv ed. Furthermore, IgM-/- mice showed increased natural killer (NK) acti vity upon exposure to either lymphocytic choriomeningitis virus (LCMV) or to poly(I). poly(C), while NK activity in untreated IgM-/- mice wa s within normal ranges. Cytotoxic T cell responses were comparable in IgM-/- and control mice infected either with VSV or with vaccinia viru s or with low doses of LCMV (10(2) infectious focus-forming units [ifu ]). After intracerebral infection with LCMV-Armstrong, CD8(+) T cell-m ediated lethal lymphocytic choriomeningitis developed independently of the presence of B cells and antibodies. After infection with high dos es (2 x 10(6) - 5 x 10(6) ifu) of LCMV-WE or LCMV-Docile, IgM-/- mice exhibited a reduced capacity to control these primary infections and h ad elevated virus titers for prolonged times (> 60 days). Nevertheless , the cytotoxic T cell response against LCMV in the early phase of inf ection was comparable in IgM-/- and control mice, but disappeared in t hose IgM-/- mice which had a persistent viral infection. Cytotoxic T c ell memory was apparently unimpaired in low-dose-primed IgM-/mice, whi ch were able to control the primary virus infection; both IgM-/- and c ontrol mice cleared a high intravenous dose of virus within 2 days aft er challenge infection. This indicates that an efficient T cell memory against LCMV was established in the absence of B cells.