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 immunoglobulin mu 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 (10(2) 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(6) - 5 x 10(6) 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.
Bründler
M A
MA
Department of Pathology, University of Zurich, Switzerland.
Aichele
P
P
Bachmann
M
M
Kitamura
D
D
Rajewsky
K
K
Zinkernagel
R M
RM
D000818:Animals; D000906:Antibodies / Q000502:physiology*; D001402:B-Lymphocytes / Q000502:physiology*; D007156:Immunologic Memory; D007694:Killer Cells, Natural / Q000276:immunology; D008216:Lymphocytic Choriomeningitis / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D011817:Rabbits; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*; D014616:Vaccinia virus / Q000276:immunology; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology; D014777:Virus Diseases / Q000276:immunology*
D000906:Antibodies