DNase I hypersensitive sites in human I epsilon region of immunoglobulin heavy chain genes abnormally induced by interleukin-4 in B-lymphocytes of atopic patients with high levels of serum IgE

J Investig Allergol Clin Immunol. 1998 Jul-Aug;8(4):234-8.

Abstract

Interleukin-4 (IL-4) induces germline C epsilon transcripts prior to C epsilon switch recombination in human B-lymphocytes. In chromatin, nucleosome-free regions known as nuclease hypersensitive sites represent the "open windows" that allow enhanced access of crucial resident cis-acting DNA sequences to transacting factors. In this study, lymphoblastoid cell lines (LCLs) were established from surface IgE negative B-cells of healthy children and patients with high levels of serum IgE, using Epstein-Barr virus. The germline C epsilon transcript was amplified from cDNA of the patients' LCLs cultured with low concentrations of recombinant interleukin-4 (rIL-4, 10 IU/ml), while it was not amplified from the cDNA of the healthy LCLs with the low concentration of rIL-4. The germline C epsilon transcript was strongly amplified from cDNA of the patients' LCLs with high concentrations of rIL-4 (100 IU/ml), compared with that of the healthy LCLs with the high concentrations of rIL-4. Moreover, the DNase I hypersensitive site of the I epsilon region was abnormally induced in the patients' LCLs even by a low concentration of rIL-4, compared with that of healthy LCLs. Our results indicate that DNase I hypersensitive sites in the I epsilon region of immunoglobulin-heavy chain genes are abnormally induced by IL-4 in the B-cells of atopic patients with high levels of serum IgE, and, as a result, the germline C epsilon transcript is abnormally expressed.

MeSH terms

  • Asthma / immunology*
  • B-Lymphocytes / drug effects*
  • Cell Line
  • Child
  • DNA Footprinting
  • Deoxyribonuclease I / metabolism*
  • Gene Expression Regulation
  • Humans
  • Immunoglobulin E / blood*
  • Immunoglobulin Heavy Chains / genetics*
  • Immunoglobulin epsilon-Chains / genetics*
  • Interleukin-4 / pharmacology*
  • Monocytes / immunology

Substances

  • Immunoglobulin Heavy Chains
  • Immunoglobulin epsilon-Chains
  • Interleukin-4
  • Immunoglobulin E
  • Deoxyribonuclease I