Interleukin-4 receptor expression by human B cells: Functional analysis with a human interleukin-4 toxin, DAB389IL-4

Haifa H. Jabara, Donata Vercelli, Lynda C. Schneider, Diane P. Williams, Frank S. Genbauffe, Louis R. Poissonb, Cory A. Waters, Raif S. Geha

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Background: Studies of human IgE-secreting B cells have proven difficult because of the small size of this population. We have used an interleukin-4 (IL-4) fusion toxin to detect functionally IL-4 receptor (IL-4R) expression on B cells involved in IgE synthesis. Methods: In diphtheria toxin IL-4 (DAB389IL-4) the receptor-binding domain of diphtheria toxin has been replaced with human IL-4. DAB389IL-4 cytotoxicity depends on IL-4R binding and internalization. Results: Addition of DAB389IL-4 inhibited IgE synthesis induced by IL-4+ anti-CD40 monoclonal antibody or hydrocortisone. IgE inhibition resulted from DAB389IL-4 B-cell cytotoxicity because DAB389IL-4 inhibited IL-4-independent B-cell proliferation. Thus induction of human IgE synthesis involves IL-4R + cells. In contrast, terminally differentiated, IgE-producing B cells no longer express functional IL-4R because DAB389IL-4 only modestly inhibited ongoing IgE synthesis by B cells from patients with hyper-IgE states and only minimally affected IL-4-induced IgE synthesis in normal B cells when the toxin was added at day 7. Pokeweed mitogen-induced IgM synthesis was sensitive to early but not to late addition of DAB389IL-4. Thus the loss of functional IL-4R immunoglobulin-secreting B cells is independent of isotype switching. Conclusions: IgE-secreting B cells no longer express functional IL-4R. Therapies for allergic disease that target the IL-4R would not affect IgE-secreting B cells but may block the recruitment of B cells into the IgE-secreting pool. For optimal benefits this approach may be combined with therapies that target IL-4R-, IgE-secreting B cells. (J A LLERGY CLIN I MMUNOL 1995;95:893-900.).

Original languageEnglish (US)
Pages (from-to)893-900
Number of pages8
JournalThe Journal of Allergy and Clinical Immunology
Volume95
Issue number4
DOIs
StatePublished - Apr 1995
Externally publishedYes

Keywords

  • IgE synthesis
  • Interleukin-4
  • diphtheria fusion toxins
  • interleukin-4 receptors

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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