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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.[1]

References

  1. 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. Kondo, N., Fukao, T., Kaneko, H., Teramoto, T., Tashita, H., Inoue, R. Journal of investigational allergology & clinical immunology : official organ of the International Association of Asthmology (INTERASMA) and Sociedad Latinoamericana de Alergia e Inmunología. (1998) [Pubmed]
 
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