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.
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.
Department of Pediatrics, Gifu University School of Medicine, Japan.
N
N
Kondo
T
T
Fukao
H
H
Kaneko
T
T
Teramoto
H
H
Tashita
R
R
Inoue
D001249:Asthma / Q000276:immunology*; D001402:B-Lymphocytes / Q000187:drug effects*; D002460:Cell Line; D002648:Child; D018983:DNA Footprinting; D003850:Deoxyribonuclease I / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007139:Immunoglobulin epsilon-Chains / Q000235:genetics*; D015847:Interleukin-4 / Q000494:pharmacology*; D009000:Monocytes / Q000276:immunology
D007143:Immunoglobulin Heavy Chains; D007139:Immunoglobulin epsilon-Chains; D015847:Interleukin-4; D007073:Immunoglobulin E; D003850:Deoxyribonuclease I