Human BLyS Facilitates Engraftment of Human PBL Derived B Cells in Immunodeficient Mice
| Autor: | Dale L. Greiner, Madelyn R. Schmidt, Michael C. Appel, Robert T. Woodland, Lisa J. Giassi, Leonard D. Shultz |
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| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Adoptive cell transfer
Lymphocyte B-cell receptor Immunology Antigens CD19 lcsh:Medicine Nod Cell Separation Mice SCID Biology Receptors Tumor Necrosis Factor Pneumococcal Vaccines 03 medical and health sciences Mice 0302 clinical medicine Immune system Antigen Mice Inbred NOD medicine Animals Humans Cell Biology/Leukocyte Signaling and Gene Expression B-cell activating factor lcsh:Science 030304 developmental biology Cell Nucleus 0303 health sciences B-Lymphocytes Multidisciplinary lcsh:R NF-kappa B Flow Cytometry Recombinant Proteins 3. Good health medicine.anatomical_structure Immunology/Immune Response lcsh:Q Ex vivo 030215 immunology Research Article Signal Transduction |
| Zdroj: | PLoS ONE PLoS ONE, Vol 3, Iss 9, p e3192 (2008) |
| ISSN: | 1932-6203 |
| Popis: | The production of fully immunologically competent humanized mice engrafted with peripheral lymphocyte populations provides a model for in vivo testing of new vaccines, the durability of immunological memory and cancer therapies. This approach is limited, however, by the failure to efficiently engraft human B lymphocytes in immunodeficient mice. We hypothesized that this deficiency was due to the failure of the murine microenvironment to support human B cell survival. We report that while the human B lymphocyte survival factor, B lymphocyte stimulator (BLyS/BAFF) enhances the survival of human B cells ex vivo, murine BLyS has no such protective effect. Although human B cells bound both human and murine BLyS, nuclear accumulation of NF-kappaB p52, an indication of the induction of a protective anti-apoptotic response, following stimulation with human BLyS was more robust than that induced with murine BLyS suggesting a fundamental disparity in BLyS receptor signaling. Efficient engraftment of both human B and T lymphocytes in NOD rag1(-/-) Prf1(-/-) immunodeficient mice treated with recombinant human BLyS is observed after adoptive transfer of human PBL relative to PBS treated controls. Human BLyS treated recipients had on average 40-fold higher levels of serum Ig than controls and mounted a de novo antibody response to the thymus-independent antigens in pneumovax vaccine. The data indicate that production of fully immunologically competent humanized mice from PBL can be markedly facilitated by providing human BLyS. |
| Databáze: | OpenAIRE |
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