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Human IG production and isotype switching in severe combined immunodeficient: human mice

(1993) JOURNAL OF IMMUNOLOGY. 151(1). p.128-137
Author
Organization
Abstract
Severe combined immunodeficient (SCID) mice were transplanted with different human fetal organs (SCID-hu mice), including thymus, liver, spleen, and omentum, and the serum levels of human IgM, IgG, IgE, and IgA were measured. In all SCID-hu mice significant levels (up to 590 ng/ml) of IgM were detected, irrespective of the organs transplanted. In contrast, IgG was present (up to 530 ng/ml) only when the fetal thymus was transplanted together with the fetal liver, indicating that the presence of human T cells is a prerequisite for in vivo isotype switching by human B cells in SCID-hu mice. Additional transplantation of fetal spleen did not significantly increase IgG levels. Human IgA and IgE were never detected in the serum of these SCID-hu mice. The peak of IgM and IgG production was observed 4 months after transplantation. At that time, analysis by IEF showed that human IgG present in SCID-hu serum was at least oligoclonal. Furthermore, all IgG subclasses were represented in the human IgG pool. Human B cells were undetectable in the peripheral blood, spleen, and bone marrow of-these SCID-hu mice; in contrast, B cells expressing CD19 could be isolated from the SCID-hu thymus. Considerable proportions of the CD19+ B cells coexpressed CD5, CD7, CD10, CD40, and CD2. These B cells spontaneously produced IgM and IgG in vitro and could be induced to switch to IgE-producing cells when cocultured with cloned activated CD4+ T cells in the presence of IL-4. Collectively, these data demonstrate that functionally mature B cells able to produce IgM and IgG in vivo, and IgE in vitro, are present in the SCID-hu human thymus.
Keywords
ENGRAFTMENT, REPERTOIRE, DIFFERENTIATION, INTERLEUKIN-4, B-CELLS, SCID-HU MOUSE, T-CELL CLONES, ANTIBODY

Citation

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MLA
Vandekerckhove, Bart et al. “Human IG Production and Isotype Switching in Severe Combined Immunodeficient: Human Mice.” JOURNAL OF IMMUNOLOGY 151.1 (1993): 128–137. Print.
APA
Vandekerckhove, B., Jones, D., Punnonen, J., Schols, D., Lin, H., Duncan, B., Bachetta, R., et al. (1993). Human IG production and isotype switching in severe combined immunodeficient: human mice. JOURNAL OF IMMUNOLOGY, 151(1), 128–137.
Chicago author-date
Vandekerckhove, Bart, D Jones, J Punnonen, D Schols, H Lin, B Duncan, R Bachetta, J Devries, and M Roncarolo. 1993. “Human IG Production and Isotype Switching in Severe Combined Immunodeficient: Human Mice.” Journal of Immunology 151 (1): 128–137.
Chicago author-date (all authors)
Vandekerckhove, Bart, D Jones, J Punnonen, D Schols, H Lin, B Duncan, R Bachetta, J Devries, and M Roncarolo. 1993. “Human IG Production and Isotype Switching in Severe Combined Immunodeficient: Human Mice.” Journal of Immunology 151 (1): 128–137.
Vancouver
1.
Vandekerckhove B, Jones D, Punnonen J, Schols D, Lin H, Duncan B, et al. Human IG production and isotype switching in severe combined immunodeficient: human mice. JOURNAL OF IMMUNOLOGY. 1993;151(1):128–37.
IEEE
[1]
B. Vandekerckhove et al., “Human IG production and isotype switching in severe combined immunodeficient: human mice,” JOURNAL OF IMMUNOLOGY, vol. 151, no. 1, pp. 128–137, 1993.
@article{628363,
  abstract     = {Severe combined immunodeficient (SCID) mice were transplanted with different human fetal organs (SCID-hu mice), including thymus, liver, spleen, and omentum, and the serum levels of human IgM, IgG, IgE, and IgA were measured. In all SCID-hu mice significant levels (up to 590 ng/ml) of IgM were detected, irrespective of the organs transplanted. In contrast, IgG was present (up to 530 ng/ml) only when the fetal thymus was transplanted together with the fetal liver, indicating that the presence of human T cells is a prerequisite for in vivo isotype switching by human B cells in SCID-hu mice. Additional transplantation of fetal spleen did not significantly increase IgG levels. Human IgA and IgE were never detected in the serum of these SCID-hu mice. The peak of IgM and IgG production was observed 4 months after transplantation. At that time, analysis by IEF showed that human IgG present in SCID-hu serum was at least oligoclonal. Furthermore, all IgG subclasses were represented in the human IgG pool. Human B cells were undetectable in the peripheral blood, spleen, and bone marrow of-these SCID-hu mice; in contrast, B cells expressing CD19 could be isolated from the SCID-hu thymus. Considerable proportions of the CD19+ B cells coexpressed CD5, CD7, CD10, CD40, and CD2. These B cells spontaneously produced IgM and IgG in vitro and could be induced to switch to IgE-producing cells when cocultured with cloned activated CD4+ T cells in the presence of IL-4. Collectively, these data demonstrate that functionally mature B cells able to produce IgM and IgG in vivo, and IgE in vitro, are present in the SCID-hu human thymus.},
  author       = {Vandekerckhove, Bart and Jones, D and Punnonen, J and Schols, D and Lin, H and Duncan, B and Bachetta, R and Devries, J and Roncarolo, M},
  issn         = {0022-1767},
  journal      = {JOURNAL OF IMMUNOLOGY},
  keywords     = {ENGRAFTMENT,REPERTOIRE,DIFFERENTIATION,INTERLEUKIN-4,B-CELLS,SCID-HU MOUSE,T-CELL CLONES,ANTIBODY},
  language     = {eng},
  number       = {1},
  pages        = {128--137},
  title        = {Human IG production and isotype switching in severe combined immunodeficient: human mice},
  volume       = {151},
  year         = {1993},
}