IL-4 induces human B cell maturation and IgE synthesis in SCID-hu mice

Inhibition of ongoing IgE production by in vivo treatment with an IL-4/IL-13 receptor antagonist

J. M. Carballido, D. Schols, R. Namikawa, S. Zurawski, G. Zurawski, M. G. Roncarolo, J. E. De Vries

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Abstract

The effect of cytokine treatment on the in vivo maturation and Ig isotype switching of human B cells was studied in a modified SCID-hu mouse model. SCID mice, subcutaneously cotransplanted with small fragments of fetal human thymus and bone (SCID-hu BM/T mice) generated all human leukocyte lineages including T and B lymphocytes, macrophages, and granulocytes. All SCID-hu BM/T mice spontaneously produced human IgM and IgG, whereas IgE and IgA were detected in 37 and 80% of the mice, respectively, indicating that productive human T-B cell interactions resulting in Ig isotype switching occur in these mice. Administration of IL-4 to SCID-hu BM/T mice enhanced human B cell maturation, as judged by the increase in the percentages of CD45+, CD19+ bone marrow B cells expressing CD20, CD23, CD40, sIgM, and sIgD. Furthermore, these cells were also functionally more mature because they spontaneously produced human IgG/IgG4 in vitro and could be induced to secrete human IgE by addition of anti-CD40 mAb alone. In contrast, B cells isolated from PBS- treated mice only produce significant Ig levels after stimulation with anti- CD40 mAb in the presence of exogenous IL-4. IL-4 administration also induced human IgE synthesis in 44% of the mice, which had no serum IgE before treatment. More importantly, ongoing human IgE synthesis in SCID-hu BM/T mice was suppressed by >90% following administration of an IL-4 mutant protein, which acts as an IL-4 and IL-13 receptor antagonist. These results suggest that IL-4/IL-13 receptor antagonists have potential clinical utility in treating human atopic diseases associated with enhanced IgE production.

Original languageEnglish
Pages (from-to)4162-4170
Number of pages9
JournalJournal of Immunology
Volume155
Issue number9
Publication statusPublished - 1995

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Interleukin-13 Receptors
SCID Mice
Interleukin-4
Immunoglobulin E
B-Lymphocytes
Immunoglobulin Class Switching
Immunoglobulin G
Mutant Proteins
Granulocytes
Cell Communication
Bone Marrow Cells
Immunoglobulin A
Thymus Gland
Immunoglobulin M

ASJC Scopus subject areas

  • Immunology

Cite this

Carballido, J. M., Schols, D., Namikawa, R., Zurawski, S., Zurawski, G., Roncarolo, M. G., & De Vries, J. E. (1995). IL-4 induces human B cell maturation and IgE synthesis in SCID-hu mice: Inhibition of ongoing IgE production by in vivo treatment with an IL-4/IL-13 receptor antagonist. Journal of Immunology, 155(9), 4162-4170.

IL-4 induces human B cell maturation and IgE synthesis in SCID-hu mice : Inhibition of ongoing IgE production by in vivo treatment with an IL-4/IL-13 receptor antagonist. / Carballido, J. M.; Schols, D.; Namikawa, R.; Zurawski, S.; Zurawski, G.; Roncarolo, M. G.; De Vries, J. E.

In: Journal of Immunology, Vol. 155, No. 9, 1995, p. 4162-4170.

Research output: Contribution to journalArticle

Carballido, JM, Schols, D, Namikawa, R, Zurawski, S, Zurawski, G, Roncarolo, MG & De Vries, JE 1995, 'IL-4 induces human B cell maturation and IgE synthesis in SCID-hu mice: Inhibition of ongoing IgE production by in vivo treatment with an IL-4/IL-13 receptor antagonist', Journal of Immunology, vol. 155, no. 9, pp. 4162-4170.
Carballido, J. M. ; Schols, D. ; Namikawa, R. ; Zurawski, S. ; Zurawski, G. ; Roncarolo, M. G. ; De Vries, J. E. / IL-4 induces human B cell maturation and IgE synthesis in SCID-hu mice : Inhibition of ongoing IgE production by in vivo treatment with an IL-4/IL-13 receptor antagonist. In: Journal of Immunology. 1995 ; Vol. 155, No. 9. pp. 4162-4170.
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abstract = "The effect of cytokine treatment on the in vivo maturation and Ig isotype switching of human B cells was studied in a modified SCID-hu mouse model. SCID mice, subcutaneously cotransplanted with small fragments of fetal human thymus and bone (SCID-hu BM/T mice) generated all human leukocyte lineages including T and B lymphocytes, macrophages, and granulocytes. All SCID-hu BM/T mice spontaneously produced human IgM and IgG, whereas IgE and IgA were detected in 37 and 80{\%} of the mice, respectively, indicating that productive human T-B cell interactions resulting in Ig isotype switching occur in these mice. Administration of IL-4 to SCID-hu BM/T mice enhanced human B cell maturation, as judged by the increase in the percentages of CD45+, CD19+ bone marrow B cells expressing CD20, CD23, CD40, sIgM, and sIgD. Furthermore, these cells were also functionally more mature because they spontaneously produced human IgG/IgG4 in vitro and could be induced to secrete human IgE by addition of anti-CD40 mAb alone. In contrast, B cells isolated from PBS- treated mice only produce significant Ig levels after stimulation with anti- CD40 mAb in the presence of exogenous IL-4. IL-4 administration also induced human IgE synthesis in 44{\%} of the mice, which had no serum IgE before treatment. More importantly, ongoing human IgE synthesis in SCID-hu BM/T mice was suppressed by >90{\%} following administration of an IL-4 mutant protein, which acts as an IL-4 and IL-13 receptor antagonist. These results suggest that IL-4/IL-13 receptor antagonists have potential clinical utility in treating human atopic diseases associated with enhanced IgE production.",
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AU - Namikawa, R.

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AU - Roncarolo, M. G.

AU - De Vries, J. E.

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