METHYLATION PATTERNS OF I ε REGION IN B CELLS STIMULATED WITH INTERLEUKIN 4 AND EPSTEIN‐BARR VIRUS IN PATIENTS WITH A HIGH LEVEL OF SERUM IgE

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Abstract
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 ε transcript, and S μ S ε recombination. The germline C e 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 e 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 ε transcript, which may be caused by the increase of opening chromatin structures because of their unmethylation in the I ε region.