Human Ig production and isotype switching in severe combined immunodeficient-human mice

Bart A E Vandekerckhove, Deborah Jones, Juha Punnonen, Dominique Schols, Hun Chi Lin, Brian Duncan, Rosa Bacchetta, Jan E. De Vries, Maria Grazia Roncarolo

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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, IgC 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 IgC 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.

Original languageEnglish
Pages (from-to)128-137
Number of pages10
JournalJournal of Immunology
Volume151
Issue number1
Publication statusPublished - Jul 1 1993

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ASJC Scopus subject areas

  • Immunology

Cite this

Vandekerckhove, B. A. E., Jones, D., Punnonen, J., Schols, D., Lin, H. C., Duncan, B., Bacchetta, R., De Vries, J. E., & Roncarolo, M. G. (1993). Human Ig production and isotype switching in severe combined immunodeficient-human mice. Journal of Immunology, 151(1), 128-137.