Epstein-Barr virus-induced human B-cell lymphoma arising in HuPBL-SCID chimeric mice: Characterization and the role of CD40 stimulation in their treatment and prevention

S. Funakoshi, M. Beckwith, W. Fanslow, D. L. Longo, William J Murphy

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

The transfer of human peripheral blood lymphocytes (huPBL) from EBV-seropositive donors into mice with severe combined immune deficiency (SCID) has been shown previously to result in the generation of human EBV-induced B-cell lymphomas. These lymphomas are similar to the aggressive lymphomas that arise clinically in immunocompromised individuals. We have assessed the p53 status of these human B-lymphomas and the clonality of cell lines established from tumors growing in the huPBL-SCID mice. While the lymphoma cell lines were demonstrated to be pauciclonal by Southern analysis, none of the lines demonstrated mutated p53 as determined by immunoprecipitation studies using antibodies specific for mutant p53. The cell lines were all positive for CD40, a marker present on normal and neoplastic B cells. Antibodies to CD40 significantly inhibited the growth of these EBV-transformed B-cell lymphomas both in vitro and in vivo. When partially purified human B cells were incubated with either anti-CD40 or anti-IgM in the presence of EBV-containing supernatants in vitro, only anti-CD40 prevented transformation by EBV. Treatment of huPBL-SCID mice with anti-CD40 also prevented the occurrence of the EBV lymphomas. However, long-term human B-cell engraftment was not inhibited as determined by the presence of serum human immunoglobulin in the chimeric mice. Overnight incubation of the huPBL with anti-CD40 did not prevent the incidence of lymphomas in huPBL-SCID chimeras suggesting that continuous exposure to anti-CD40 is required. These studies suggest that anti-CD40 may be of significant clinical use in the treatment or prevention of EBV-induced B-cell lymphomas.

Original languageEnglish (US)
Pages (from-to)133-142
Number of pages10
JournalPathobiology
Volume63
Issue number3
StatePublished - 1995
Externally publishedYes

Keywords

  • B lymphoma
  • CD40
  • Epstein-Barr virus
  • Lymphomagenesis
  • p53
  • SCID mice

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Biochemistry
  • Immunology and Allergy
  • Cell Biology

Fingerprint Dive into the research topics of 'Epstein-Barr virus-induced human B-cell lymphoma arising in HuPBL-SCID chimeric mice: Characterization and the role of CD40 stimulation in their treatment and prevention'. Together they form a unique fingerprint.

Cite this