The Journal of Immunology, Vol 149, Issue 8 2830-2836, Copyright © 1992 by American Association of Immunologists

ARTICLES

Engraftment of human peripheral blood leukocytes into severe combined immunodeficient mice results in the long term and dynamic production of human xenoreactive antibodies

SS Williams, T Umemoto, H Kida, EA Repasky and RB Bankert
Department of Molecular Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263.

Severe combined immunodeficient (SCID) mice engrafted with human peripheral blood leukocytes (hu-PBL-SCID) represent a potentially important small animal model for the study of human immune function. Attempts to generate human primary immune responses to exogenous Ag in the hu-PBL-SCID have had limited success which raises questions about the functional capacity of human lymphocytes in the SCID environment. Here, we demonstrate that the spontaneously secreted human Ig in hu-PBL- SCID includes antibodies with specificity for several different mouse RBC (mRBC) proteins. These antibodies apparently reflect the transfer of peripheral B cells which are responsible for the production of naturally occurring xenoreactive antibodies in the donor. Western blot analysis showed that engraftment of anti-mRBC specificities was random among mice receiving PBL from the same donor sample. In at least one mouse, this engraftment was polyclonal and included human IgM and IgG which recognized at least 12 different mRBC proteins ranging in size from 35 to > 200 kDa. Anti-mRBC specificities were found to vary with time demonstrating a dynamic expression of the human xenoreactive repertoire in hu-PBL-SCID. In contrast to mice engrafted with human PBL, mice engrafted with another source of human B cells, i.e., tumor- infiltrating leukocytes, produced very little or no human anti-mRBC antibody. Ag-driven proliferation of xenoreactive clones may result in a skewing of the engrafted human B cells in hu-PBL-SCID which could account in part for the limited ability of hu-PBL-SCID to respond to exogenous Ag. The long term production of anti-mRBC antibodies and the modulation of the expressed xenoreactive repertoire observed in hu-PBL- SCID represents an opportunity to study the molecular genetics and cell biology of the human humoral immune response to a defined complex Ag.

This article has been cited by other articles:

				M. R. Simpson-Abelson, G. F. Sonnenberg, H. Takita, S. J. Yokota, T. F. Conway Jr., R. J. Kelleher Jr., L. D. Shultz, M. Barcos, and R. B. Bankert Long-Term Engraftment and Expansion of Tumor-Derived Memory T Cells Following the Implantation of Non-Disrupted Pieces of Human Lung Tumor into NOD-scid IL2R{gamma}null Mice J. Immunol., May 15, 2008; 180(10): 7009 - 7018. [Abstract] [Full Text] [PDF]

				K. F. May Jr, S. Roychowdhury, D. Bhatt, E. Kocak, X.-F. Bai, J.-Q. Liu, A. K. Ferketich, E. W. Martin Jr, M. A. Caligiuri, P. Zheng, et al. Anti-human CTLA-4 monoclonal antibody promotes T-cell expansion and immunity in a hu-PBL-SCID model: a new method for preclinical screening of costimulatory monoclonal antibodies Blood, February 1, 2005; 105(3): 1114 - 1120. [Abstract] [Full Text] [PDF]

				S. Depraetere, L. Verhoye, G. Leclercq, and G. Leroux-Roels Human B Cell Growth and Differentiation in the Spleen of Immunodeficient Mice J. Immunol., March 1, 2001; 166(5): 2929 - 2936. [Abstract] [Full Text] [PDF]

				M. Sugano, N. K. Egilmez, S. J. Yokota, F.-A. Chen, J. Harding, S. K. Huang, and R. B. Bankert Antibody Targeting of Doxorubicin-loaded Liposomes Suppresses the Growth and Metastatic Spread of Established Human Lung Tumor Xenografts in Severe Combined Immunodeficient Mice Cancer Res., December 1, 2000; 60(24): 6942 - 6949. [Abstract] [Full Text]

				H. H. Donze, J. E. Cummins Jr., R. S. Schwiebert, P. N. Fultz, S. Jackson, and J. Mestecky Human and Nonhuman Primate Lymphocytes Engrafted into SCID Mice Reside in Unique Mesenteric Lymphoid Structures J. Immunol., August 1, 1998; 161(3): 1306 - 1312. [Abstract] [Full Text] [PDF]

				V. Coppola, A. Veronesi, S. Indraccolo, F. Calderazzo, M. Mion, S. Minuzzo, G. Esposito, D. Mauro, B. Silvestri, P. Gallo, et al. Lymphoproliferative Disease in Human Peripheral Blood Mononuclear Cell-Injected SCID Mice. IV. Differential Activation of Human Th1 and Th2 Lymphocytes and Influence of the Atopic Status on Lymphoma Development J. Immunol., March 1, 1998; 160(5): 2514 - 2522. [Abstract] [Full Text] [PDF]