Human adult tonsil xenotransplantation into SCID mice for studying human immune responses and B cell lymphomagenesis

Michel A. Duchosal, Marie Thérèse Fuzzati-Armentero, Roberto Baccala, Andreas Layer, Rosana Gonzalez-Quintial, Didier Leturcq, Marlies Rüegg, Philippe Trouillet, Sandrine Mauray, Jean Daniel Tissot, Marc Schapira

Research output: Contribution to journalArticlepeer-review

Abstract

Objective. To generate a human-mouse xenochimeric model where human cells remain clustered in the animal to optimize their interactions and recovery. Materials and methods. Severe combined immune deficient mice (SCID) were xenografted subcutaneously with human adult tonsil pieces (hu-ton-SCID mice). Such animals were: (a) compared with those receiving tonsil cells in suspension, and (b) immunized with de novo and recall antigens. Results. Human tonsil pieces survived a long period of time in SCID mice, while polyclonal human T- and B-lymphocytes persisted in close vicinity within the implantation area; however, little or no graft-versus-host disease was detectable. Not surprisingly, local development of lymphoproliferative disease was often observed in animals receiving lymphoid implants from donors previously infected by the Epstein-Barr virus. One month after surgery, higher serum levels of human IgG were found in SCID mice transplanted with tonsil pieces (2 x 107 cells/animal) than in animals injected with 5 x 107 tonsil cells in suspension (1.9 vs. 0.3 mg/mL, p <0.002). Importantly, the production of human IgG in hu-ton-SCID mice remained polyclonal for at least 6 months and was linked to the presence of cells within the implants. Immunization of hu-ton-SCID mice with hepatitis B core, a de novo antigen, did not produce a significant IgG immune response; however immunization with tetanus toxoid (TT), a thymus-dependent recall antigen, yielded high (> 700- fold increase in anti-TT IgG levels) and long-lasting (> 6 months) secondary immune responses. Conclusion. The hu-ton-SCID mouse xenochimeric model described in this report may improve our understanding of human lymphoid cell interactions, secondary immune responses, and lymphomagenesis. (C) 2000 International Society for Experimental Hematology.

Original languageEnglish
Pages (from-to)177-192
Number of pages16
JournalExperimental Hematology
Volume28
Issue number2
DOIs
Publication statusPublished - Feb 2000

Keywords

  • Human tonsil
  • Immune response
  • Severe combined immune deficiency mouse
  • Xenotransplantation

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

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