1alpha,25-dihydroxyvitamin D3 inhibits anti-CD40 plus IL-4-mediated IgE production in vitro

Eur J Immunol. 2002 Dec;32(12):3395-404. doi: 10.1002/1521-4141(200212)32:12<3395::AID-IMMU3395>3.0.CO;2-#.


In the present study, we examined whether anti-CD40+IL-4-mediated B cell proliferation and immunoglobulin synthesis is affected by vitamin D (VD) and its low-hypercalcemic analogue EB1089 in Bcells from healthy donors. Analysis of vitamin D receptor (VDR) expression showed that only anti-CD40+IL-4-stimulated, but not resting B cells express VDR. Studies on B cell proliferation revealed that anti-CD40+IL-4-mediated proliferation of B cells was not affected by VD or EB1089. By contrast, IgE synthesis was markedly inhibited by both, VD and EB1089, starting at concentrations from 10(-10) M for VD and 10(-12) M for EB1089, with maximal inhibition at 10(-6) M (VD 85.5+/-9.7%; EB1089 77.3+/-10.8%). The production of the other Ig (IgA and IgG) was not significantly inhibited by VD after anti-CD40+IL-4 stimulation, and IgM production was only slightly reduced (18.7+/-7.9%). These observations were confirmed by intracellular staining of the different isotypes in B cells after anti-CD40+IL-4 stimulation, which showed a strong reduction of IgE(+) cells in the presence of VD. Analyses of molecules that are known to affect IgE production (CD23 and IL-6) revealed that these are not involved in VD-dependent inhibition of IgE production. By contrast, epsilon germ-line transcription was inhibited by VD (41.2+/-26.1%; n=5), as was NF-kappaB (p50 and p65) protein expression in stimulated cells. These data show that VD and its analogue EB1089 inhibit IgE production of anti-CD40+IL-4-stimulated B cells in vitro. The involved mechanism includes epsilon germ-line transcription, NF-kappaB activation and switch recombination suggesting that complex mechanisms of VD action in anti-CD40+IL-4-stimulated B cells are responsible.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / immunology*
  • Base Sequence
  • CD40 Antigens / immunology*
  • Calcitriol / analogs & derivatives*
  • Calcitriol / pharmacology*
  • DNA / genetics
  • Humans
  • Immunoglobulin E / biosynthesis*
  • Immunoglobulin E / genetics
  • Immunoglobulin epsilon-Chains / genetics
  • In Vitro Techniques
  • Interleukin-4 / metabolism*
  • Interleukin-6 / metabolism
  • Receptors, Calcitriol / metabolism
  • Receptors, IgE / metabolism
  • Transcription, Genetic / drug effects


  • CD40 Antigens
  • Immunoglobulin epsilon-Chains
  • Interleukin-6
  • Receptors, Calcitriol
  • Receptors, IgE
  • Interleukin-4
  • Immunoglobulin E
  • DNA
  • Calcitriol
  • seocalcitol