Human BLyS facilitates engraftment of human PBL derived B cells in immunodeficient mice.
Antigens-CD19, B-Lymphocytes, Cell-Nucleus, Cell-Separation, Flow-Cytometry, Mice-Inbred-NOD, Mice-SCID, NF-kappa-B, Pneumococcal-Vaccines, Receptors-Tumor-Necrosis-Factor, Recombinant-Proteins, Signal-Transduction
PLoS ONE 2008; 3(9):e3192.
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.
Schmidt, M R.; Appel, M C.; Giassi, L J.; Greiner, D L.; Shultz, L D.; and Woodland, R T., "Human BLyS facilitates engraftment of human PBL derived B cells in immunodeficient mice." (2008). Faculty Research 2000 - 2009. 1842.