Abstract
Mice with severe combined immunodeficiency (C.B-17 scid, hereafter SCID) accept xenografts of adult human peripheral blood leukocytes (PBL). The transplanted human PBL expand in number and survive for at least thirteen months and have been shown to reconstitute human immune function at both the T and B cell levels. Human immunoglobulin production is restored, and secondary antibody responses to antigens such as tetanus toxoid can be induced. All SCID mice reconstituted with 50 × 106 or more PBL from donors with evidence of exposure to Epstein-Barr virus (EBV) have developed human B cell lymphomas at 8–16 weeks after PBL engraftment, whereas mice reconstituted with PBL from EBV-seronegative donors fail to develop tumors. These tumors involve both lymphatic and non-lymphatic organs, and histologically they resemble large cell or immunoblastic lymphomas. The tumors are associated with high levels of human immunoglobulin secretion and serum electrophoresis reveals oligoclonal immunoglobulin banding patterns. Analysis of tumor DNA shows the presence of EBV genomes and oligoclonal patterns of immunoglobulin JH gene rearrangement. Taken together, these observations suggest an EBV-related proliferation of B lymphocytes leading to the rapid appearance of oligoclonal B cell malignancies following transfer of B lymphocytes from “normal” donors to SCID mice.
SCID mice reconstituted with PBL from EBV-seronegative donors have been infected with the LAV-1 strain of human immunodeficiency virus (HIV-1). Virus has been recovered from most infected animals by co-culture of mouse tissue with human T lymphoblasts. Some mice with high virus titers have developed an acute wasting syndrome and depletion of human T cells. These preliminary results suggest the use of HIV-infected human PBL-reconstituted SCID mice as a small animal model for AIDS research.
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© 1989 Springer-Verlag Berlin · Heidelberg
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Mosier, D.E. et al. (1989). Studies of HIV Infection and the Development of Epstein-Barr Virus-Related B Cell Lymphomas Following Transfer of Human Lymphocytes to Mice With Severe Combined Immunodeficiency. In: Bosma, M.J., Phillips, R.A., Schuler, W. (eds) The Scid Mouse. Current Topics in Microbiology and Immunology, vol 152. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-74974-2_23
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DOI: https://doi.org/10.1007/978-3-642-74974-2_23
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-74976-6
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