Skip to main content
NCBI home page
Immunology logoLink to Immunology
. 1994 Oct;83(2):163–170.

The in vivo production of specific human antibodies by vaccination of human-PBL-SCID mice.

W Walker 1, G Gallagher 1
PMCID: PMC1414952  PMID: 7530687

Abstract

Human-PBL-SCID animals were created by intraperitoneal (i.p.) transfer of human peripheral blood lymphocytes (PBL) or PBL depleted of CD8-expressing lymphocytes (CD8dL). Analysis of human immunoglobulin levels in these animals revealed that severe combined immunodeficiency (SCID) mice receiving CD8dL produced significantly higher levels of serum human immunoglobulin than those receiving PBL. In an attempt to induce antigen-specific human antibodies these human-PBL-SCID animals were vaccinated with soluble protein antigen [ovalbumin (OVA)] entrapped within liposomes as an immunological adjuvant. Vaccination produced antigen-specific human IgM and IgG in human-PBL-SCID mouse serum. The use of liposomes as adjuvant and the reconstitution of animals with CD8dL together enhanced the OVA-specific immune response as evidenced by the detection of significantly increased serum antibody titres. In the CD8dL reconstituted group, solid tumours of human B-cell origin became detectable in the peritoneal cavity of animals at 8-10 weeks post-reconstitution. These tumours were readily established in vitro and subsequent analysis of culture supernatants showed that these malignant cells continue to secrete human antibodies specific for the original immunizing antigen in vitro. We believe this vaccination of the human-PBL-SCID mouse to produce antigen-specific human antibodies, may find use in the future production of human monoclonal antibodies and in the testing and development of novel vaccine/adjuvant systems.

Full text

PDF
163

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abedi M. R., Christensson B., Islam K. B., Hammarström L., Smith C. I. Immunoglobulin production in severe combined immunodeficient (SCID) mice reconstituted with human peripheral blood mononuclear cells. Eur J Immunol. 1992 Mar;22(3):823–828. doi: 10.1002/eji.1830220329. [DOI] [PubMed] [Google Scholar]
  2. Allison A. G., Gregoriadis G. Liposomes as immunological adjuvants. Nature. 1974 Nov 15;252(5480):252–252. doi: 10.1038/252252a0. [DOI] [PubMed] [Google Scholar]
  3. Armstrong N., Cigel F., Borcherding W., Hong R., Malkovska V. In vitro preactivated human T cells engraft in SCID mice and migrate to murine lymphoid tissues. Clin Exp Immunol. 1992 Dec;90(3):476–482. doi: 10.1111/j.1365-2249.1992.tb05870.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bosma G. C., Custer R. P., Bosma M. J. A severe combined immunodeficiency mutation in the mouse. Nature. 1983 Feb 10;301(5900):527–530. doi: 10.1038/301527a0. [DOI] [PubMed] [Google Scholar]
  5. Boyd J. E., James K. Human monoclonal antibodies: their potential, problems, and prospects. Adv Biotechnol Processes. 1989;11:1–43. [PubMed] [Google Scholar]
  6. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  7. Brewer J. M., Alexander J. The adjuvant activity of non-ionic surfactant vesicles (niosomes) on the BALB/c humoral response to bovine serum albumin. Immunology. 1992 Apr;75(4):570–575. [PMC free article] [PubMed] [Google Scholar]
  8. Carlsson R., Mårtensson C., Kalliomäki S., Ohlin M., Borrebaeck C. A. Human peripheral blood lymphocytes transplanted into SCID mice constitute an in vivo culture system exhibiting several parameters found in a normal humoral immune response and are a source of immunocytes for the production of human monoclonal antibodies. J Immunol. 1992 Feb 15;148(4):1065–1071. [PubMed] [Google Scholar]
  9. Cavacini L. A., Kennel M., Lally E. V., Posner M. R., Quinn A. Human immunoglobulin production in immunodeficient mice: enhancement by immunosuppression of host and in vitro activation of human mononuclear cells. Clin Exp Immunol. 1992 Oct;90(1):135–140. doi: 10.1111/j.1365-2249.1992.tb05845.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Duchosal M. A., Eming S. A., Fischer P., Leturcq D., Barbas C. F., 3rd, McConahey P. J., Caothien R. H., Thornton G. B., Dixon F. J., Burton D. R. Immunization of hu-PBL-SCID mice and the rescue of human monoclonal Fab fragments through combinatorial libraries. Nature. 1992 Jan 16;355(6357):258–262. doi: 10.1038/355258a0. [DOI] [PubMed] [Google Scholar]
  11. Fiorentino D. F., Zlotnik A., Vieira P., Mosmann T. R., Howard M., Moore K. W., O'Garra A. IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th1 cells. J Immunol. 1991 May 15;146(10):3444–3451. [PubMed] [Google Scholar]
  12. Klein G. Viral latency and transformation: the strategy of Epstein-Barr virus. Cell. 1989 Jul 14;58(1):5–8. doi: 10.1016/0092-8674(89)90394-2. [DOI] [PubMed] [Google Scholar]
  13. Lieber M. R., Hesse J. E., Lewis S., Bosma G. C., Rosenberg N., Mizuuchi K., Bosma M. J., Gellert M. The defect in murine severe combined immune deficiency: joining of signal sequences but not coding segments in V(D)J recombination. Cell. 1988 Oct 7;55(1):7–16. doi: 10.1016/0092-8674(88)90004-9. [DOI] [PubMed] [Google Scholar]
  14. Macht L. M., Corrall R. J., Banga J. P., Elson C. J. Control of human thyroid autoantibody production in SCID mice. Clin Exp Immunol. 1993 Mar;91(3):390–396. doi: 10.1111/j.1365-2249.1993.tb05914.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Miltenyi S., Müller W., Weichel W., Radbruch A. High gradient magnetic cell separation with MACS. Cytometry. 1990;11(2):231–238. doi: 10.1002/cyto.990110203. [DOI] [PubMed] [Google Scholar]
  16. Morrison S. L. In vitro antibodies: strategies for production and application. Annu Rev Immunol. 1992;10:239–265. doi: 10.1146/annurev.iy.10.040192.001323. [DOI] [PubMed] [Google Scholar]
  17. Mosier D. E., Gulizia R. J., Baird S. M., Wilson D. B. Transfer of a functional human immune system to mice with severe combined immunodeficiency. Nature. 1988 Sep 15;335(6187):256–259. doi: 10.1038/335256a0. [DOI] [PubMed] [Google Scholar]
  18. Mowat A. M., Maloy K. J., Donachie A. M. Immune-stimulating complexes as adjuvants for inducing local and systemic immunity after oral immunization with protein antigens. Immunology. 1993 Dec;80(4):527–534. [PMC free article] [PubMed] [Google Scholar]
  19. Mueller B. M., Reisfeld R. A. Potential of the scid mouse as a host for human tumors. Cancer Metastasis Rev. 1991 Oct;10(3):193–200. doi: 10.1007/BF00050791. [DOI] [PubMed] [Google Scholar]
  20. Ohlin M., Danielsson L., Carlsson R., Borrebaeck C. A. The effect of leucyl-leucine methyl ester on proliferation and Ig secretion of EBV-transformed human B lymphocytes. Immunology. 1989 Apr;66(4):485–490. [PMC free article] [PubMed] [Google Scholar]
  21. Rowe M., Young L. S., Crocker J., Stokes H., Henderson S., Rickinson A. B. Epstein-Barr virus (EBV)-associated lymphoproliferative disease in the SCID mouse model: implications for the pathogenesis of EBV-positive lymphomas in man. J Exp Med. 1991 Jan 1;173(1):147–158. doi: 10.1084/jem.173.1.147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Saxon A., Macy E., Denis K., Tary-Lehmann M., Witte O., Braun J. Limited B cell repertoire in severe combined immunodeficient mice engrafted with peripheral blood mononuclear cells derived from immunodeficient or normal humans. J Clin Invest. 1991 Feb;87(2):658–665. doi: 10.1172/JCI115043. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Schuler W., Weiler I. J., Schuler A., Phillips R. A., Rosenberg N., Mak T. W., Kearney J. F., Perry R. P., Bosma M. J. Rearrangement of antigen receptor genes is defective in mice with severe combined immune deficiency. Cell. 1986 Sep 26;46(7):963–972. doi: 10.1016/0092-8674(86)90695-1. [DOI] [PubMed] [Google Scholar]
  24. Shek P. N., Sabiston B. H. Immune response mediated by liposome-associated protein antigens. I. Potentiation of the plaque-forming cell response. Immunology. 1982 Feb;45(2):349–356. [PMC free article] [PubMed] [Google Scholar]
  25. Tary-Lehmann M., Saxon A. Human mature T cells that are anergic in vivo prevail in SCID mice reconstituted with human peripheral blood. J Exp Med. 1992 Feb 1;175(2):503–516. doi: 10.1084/jem.175.2.503. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Tosato G., Steinberg A. D., Yarchoan R., Heilman C. A., Pike S. E., De Seau V., Blaese R. M. Abnormally elevated frequency of Epstein-Barr virus-infected B cells in the blood of patients with rheumatoid arthritis. J Clin Invest. 1984 Jun;73(6):1789–1795. doi: 10.1172/JCI111388. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Van Rooijen N. The liposome-mediated macrophage 'suicide' technique. J Immunol Methods. 1989 Nov 13;124(1):1–6. doi: 10.1016/0022-1759(89)90178-6. [DOI] [PubMed] [Google Scholar]
  28. Vladutiu A. O. The severe combined immunodeficient (SCID) mouse as a model for the study of autoimmune diseases. Clin Exp Immunol. 1993 Jul;93(1):1–8. doi: 10.1111/j.1365-2249.1993.tb06488.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Winter G., Milstein C. Man-made antibodies. Nature. 1991 Jan 24;349(6307):293–299. doi: 10.1038/349293a0. [DOI] [PubMed] [Google Scholar]
  30. de Waal Malefyt R., Haanen J., Spits H., Roncarolo M. G., te Velde A., Figdor C., Johnson K., Kastelein R., Yssel H., de Vries J. E. Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression. J Exp Med. 1991 Oct 1;174(4):915–924. doi: 10.1084/jem.174.4.915. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES