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T cell-independent antibody-mediated clearance of polyoma virus in T cell-deficient mice
E Szomolanyi-Tsuda1, R M Welsh
1Department of Pathology, University of Massachusetts Medical Center, Worcester 01655, USA.
Abstract:
Polyomavirus (PyV) infection of SCID mice, which lack functional T and B cells, leads to a lethal acute myeloproliferative disease (AMD) and to high levels of virus replication in several organs by two wk after infection. This is in contrast to infection of T cell-deficient athymic nude mice, which are resistant to acute PyV-induced disease and poorly replicate the virus in their organs. This major difference in the virus load and in the outcome of PyV infection between SCID and nude mice suggested that an efficient, T cell-independent antiviral mechanism operates in T cell-deficient, PyV infected mice. To investigate this possibility, mice with different genetically engineered T and/or B cell deficiencies and SCID mice adoptively reconstituted with B and/or T cells were infected with PyV. The results indicated that the presence of B cells in the absence of T cells protected mice from the AMD, and this was accompanied by a major reduction of PyV in all organs tested. Sera from PyV-infected T cell receptor (TCR) alpha beta knockout or TCR alpha beta gamma delta knockout mice contained IgG2a antibodies to PyV. Sera or purified immunoglobulin fractions from PyV-infected TCR alpha beta knockout mice protected SCID mice from the PyV-induced AMD. To our knowledge, this is the first report of an effective T cell-independent antibody response clearing a virus and changing the outcome of infection from 100% mortality to 100% survival.
Insights
B cells alone can mount an effective T cell-independent antiviral response against Polyomavirus (PyV), preventing lethal disease and clearing the virus. This antibody-mediated immunity offers complete protection in mice.
Area of Science:
- Immunology
- Virology
Background:
- Severe combined immunodeficiency (SCID) mice infected with Polyomavirus (PyV) develop lethal acute myeloproliferative disease (AMD).
- T cell-deficient athymic nude mice are resistant to PyV-induced AMD and exhibit low viral loads, suggesting a T cell-independent antiviral mechanism.
Purpose of the Study:
- To investigate the role of B cells in T cell-independent antiviral immunity against PyV.
- To determine if B cell-produced antibodies can protect against PyV-induced lethal disease.
Main Methods:
- Infection of mice with varying T and B cell deficiencies (including SCID mice reconstituted with B cells) with PyV.
- Analysis of viral load and disease outcome.
- Detection of PyV-specific antibodies (IgG2a) in knockout mouse sera.
- Passive transfer of PyV-immune sera or immunoglobulins to SCID mice.
Main Results:
- B cells, in the absence of T cells, protected mice from PyV-induced AMD and significantly reduced viral replication.
- PyV-infected T cell receptor (TCR) knockout mice produced PyV-specific IgG2a antibodies.
- Passive transfer of antibodies from PyV-infected mice conferred complete protection against lethal PyV-induced AMD in SCID mice.
Conclusions:
- This study demonstrates the first effective T cell-independent antibody response capable of clearing a virus.
- B cell-mediated antibody production is sufficient to protect against severe PyV infection and lethality.
- This finding redefines our understanding of antiviral immunity, highlighting the critical role of B cells in the absence of T cell help.