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

J Allergy Clin Immunol. 1995 Apr;95(4):893-900. doi: 10.1016/s0091-6749(95)70134-6.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • B-Lymphocytes / drug effects
  • B-Lymphocytes / metabolism*
  • Diphtheria Toxin / administration & dosage
  • Diphtheria Toxin / pharmacology*
  • Humans
  • Immunoglobulin Class Switching
  • Immunoglobulin E / biosynthesis
  • Interleukin-4 / administration & dosage
  • Interleukin-4 / metabolism
  • Interleukin-4 / pharmacology*
  • Protein Synthesis Inhibitors / pharmacology
  • Receptors, Interleukin / metabolism*
  • Receptors, Interleukin-4
  • Recombinant Fusion Proteins
  • T-Lymphocytes / physiology
  • Time Factors


  • DAB(389)-interleukin 4
  • Diphtheria Toxin
  • Protein Synthesis Inhibitors
  • Receptors, Interleukin
  • Receptors, Interleukin-4
  • Recombinant Fusion Proteins
  • Interleukin-4
  • Immunoglobulin E