METHYLATION PATTERNS OF I-EPSILON REGION IN B-CELLS STIMULATED WITH INTERLEUKIN-4 AND EPSTEIN-BARR-VIRUS IN PATIENTS WITH A HIGH-LEVEL OF SERUM IGE

Human IgE synthesis requires the presence of both interleukin 4 (IL-4) and T-cells. However, it is not clear what role IL-4 and T-cells play in the induction of IgE synthesis at the level of gene regulation. B cells that were obtained from patients with a high level of serum IgE and from healthy donors were immortalized by Epstein-Barr virus. We examined IgE production of these B cells stimulated with IL-4. Supernatant IgE levels of patient's B cells cultured with or without IL-4 were higher than those of healthy donor's B cells. Our results indicated that B cells stimulated with IL-4 from patients produced IgE, germline C epsilon transcript, and S mu S epsilon recombination. The germline C epsilon transcript was dose-dependently induced in the presence of IL-4 and related to the supernatant IgE level. In B cells stimulated with IL-4 that were obtained from patients, (some of the) DNA near or within the I epsilon region was (already partly) unmethylated, unlike those from healthy donors, and there was a loss of methyl groups of the DNA upon the addition of IL-4 in B cells from both patients and normal donors. IgE synthesis of B cells stimulated with IL-4 in patients with a high level of serum IgE is due to an accessibility in the immunoglobulin heavy-chain isotype switch, and this may reflect the accessibility in synthesis of germline C epsilon transcript, which may be caused by the increase of opening chromatin structures because of their unmethylation in the I epsilon region.