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 ex amined IgE production of these B cells stimulated with IL-4. Supernata nt 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 th at 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 with in the I epsilon region was (already partly) unmethylated, unlike thos e from healthy donors, and there was a loss of methyl groups of the DN A upon the addition of IL-4 in B cells from both patients and normal d onors. 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 immunoglob ulin heavy-chain isotype switch, and this may reflect the accessibilit y in synthesis of germline C epsilon transcript, which may be caused b y the increase of opening chromatin structures because of their unmeth ylation in the I epsilon region.