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 cell 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.
Kuwabara
N
N
Department of Pediatrics, Gifu University School of Medicine, Japan.
Kondo
N
N
Fukutomi
O
O
Fujii
H
H
Orii
T
T
D001249:Asthma / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D001483:Base Sequence; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D002648:Child; D002675:Child, Preschool; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D005812:Genes, Switch; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D007127:Immunoglobulin Constant Regions; D007073:Immunoglobulin E / Q000097:blood / Q000235:genetics*; D015847:Interleukin-4 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008745:Methylation; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction
D018076:DNA, Complementary; D007127:Immunoglobulin Constant Regions; D015847:Interleukin-4; D007073:Immunoglobulin E