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

Eur J Immunol. 1996 Sep;26(9):2257-62. doi: 10.1002/eji.1830260943.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / physiology*
  • B-Lymphocytes / physiology*
  • Immunologic Memory*
  • Killer Cells, Natural / immunology
  • Lymphocytic Choriomeningitis / immunology
  • Mice
  • Mice, Inbred C57BL
  • Rabbits
  • T-Lymphocytes, Cytotoxic / physiology*
  • Vaccinia virus / immunology
  • Vesicular stomatitis Indiana virus / immunology
  • Virus Diseases / immunology*

Substances

  • Antibodies