Regulation of immunoglobulin (Ig)E synthesis in the hyper-IgE syndrome

D. Vercelli, H. H. Jabara, C. Cunningham-Rundles, J. S. Abrams, D. B. Lewis, J. Meyer, L. C. Schneider, D. Y.M. Leung, R. S. Geha

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

The hyper-IgE (HIE) syndrome is characterized by high IgE serum levels, chronic dermatitis, and recurrent infections. The mechanisms responsible for hyperproduction IgE in HIE patients are presently unknown. We investigated whether spontaneous in vitro IgE synthesis by PBMC from seven HIE patients was sensitive to signals (cell adhesion, T/B cell cognate interaction and lymphokines: IL-4, IL-6, and IFN-γ) known to regulate IgE induction in normals. Our results show that, unlike IL-4 dependent IgE synthesis induced in normals, spontaneous IgE production by PBMC from HIE patients was not blocked by monoclonal antibodies to CD2, CD4, CD3, and MHC class II antigens. Furthermore, antibodies to IL-4 and IL-6 did not significantly suppress IgE production. IFN-γ had no significant effects on spontaneous in vitro IgE synthesis. To test whether an imbalance in lymphokine production might underlie hyperproduction of IgE in HIE patients, mitogen-induced secretion of IL-4 and IFN-γ by PBMC was assessed. No significant difference was detected between HIE patients and normal controls. Thus, ongoing IgE synthesis in the HIE syndrome is largely independent of cell-cell interactions and endogenous lymphokines, and is due to a terminally differentiated B cell population, no longer sensitive to regulatory signals.

Original languageEnglish (US)
Pages (from-to)1666-1671
Number of pages6
JournalJournal of Clinical Investigation
Volume85
Issue number5
DOIs
StatePublished - Jan 1 1990
Externally publishedYes

Keywords

  • B cell differentiation
  • cell-cell interactions
  • interferon-γ
  • interleukin 4
  • interleukin 6

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Regulation of immunoglobulin (Ig)E synthesis in the hyper-IgE syndrome'. Together they form a unique fingerprint.

  • Cite this

    Vercelli, D., Jabara, H. H., Cunningham-Rundles, C., Abrams, J. S., Lewis, D. B., Meyer, J., Schneider, L. C., Leung, D. Y. M., & Geha, R. S. (1990). Regulation of immunoglobulin (Ig)E synthesis in the hyper-IgE syndrome. Journal of Clinical Investigation, 85(5), 1666-1671. https://doi.org/10.1172/JCI114618