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 t switch recombination in human B-lymphocytes. In chromatin, nucleosom e-free regions known as nuclease hypersensitive sites represent the '' open windows'' that allow enhanced access of crucial resident cis-acti ng 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 CE 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 germ line CE transcript was strongly amplified from cDNA of the patients' L CLs with high concentrations of rIL-4 (100 IU/ml), compared with that of the healthy LCLs with the high concentrations of rIL-4. Moreover th e DNase I hypersensitive site of the IE region was abnormally induced in the patients' LCLs even by a low concentration of rIL-4, compared w ith that of healthy LCLs. Our results indicate that DNase I hypersensi tive 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 tr anscript is abnormally expressed.