High resolution analysis of the chromatin landscape of the IgE switch region in human B cells

• Published in: PloS one 2011-09, Vol.6 (9), p.e24571
• Main Authors: Dayal, Sandeep, Nedbal, Jakub, Hobson, Philip, Cooper, Alison M, Gould, Hannah J, Gellert, Martin, Felsenfeld, Gary, Fear, David J
• Format: Article
• Language: English
• Subjects: Acetylation; Adolescent; Allergies; Analysis; Antibodies; Antigens; Asthma; B cells; B-Lymphocytes - cytology; B-Lymphocytes - drug effects; B-Lymphocytes - metabolism; Biology; Biophysics; CD40 antigen; CD40 Antigens - metabolism; Cell Differentiation - drug effects; Cell Differentiation - genetics; Cell Line; Child; Child, Preschool; Chromatin; Chromatin - drug effects; Chromatin - genetics; Chromatin Assembly and Disassembly - drug effects; Chromatin Assembly and Disassembly - genetics; Class switching; Councils; Cytidine deaminase; Deoxyribonucleic acid; Diabetes; DNA; DNA binding proteins; DNA methylation; Enzymes; Genes; Genetic Loci - drug effects; Genetic Loci - genetics; Genomes; High resolution; Histone H3; Histones; Humans; Immune response; Immune system; Immunoglobulin A; Immunoglobulin E; Immunoglobulin E - genetics; Immunoglobulin G; Immunoglobulin Switch Region - drug effects; Immunoglobulin Switch Region - genetics; Immunoglobulins; Interleukin 4; Interleukin-4 - pharmacology; Isotypes; Kidney diseases; Laboratories; Lymphocytes B; Lymphocytes T; Lysine; Medical research; Medicine; Methylation; Molecular biology; Mutation; Nucleosomes; Palatine Tonsil - immunology; Recombination; Recombination, Genetic - drug effects; Recombination, Genetic - genetics; Splicing; T cells; Transcription, Genetic - drug effects; Transcription, Genetic - genetics
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0024571

Antibodies are assembled by a highly orchestrated series of recombination events during B cell development. One of these events, class switch recombination, is required to produce the IgG, IgE and IgA antibody isotypes characteristic of a secondary immune response. The action of the enzyme activation induced cytidine deaminase is now known to be essential for the initiation of this recombination event. Previous studies have demonstrated that the immunoglobulin switch regions acquire distinct histone modifications prior to recombination. We now present a high resolution analysis of these histone modifications across the IgE switch region prior to the initiation of class switch recombination in primary human B cells and the human CL-01 B cell line. These data show that upon stimulation with IL-4 and an anti-CD40 antibody that mimics T cell help, the nucleosomes of the switch regions are highly modified on histone H3, accumulating acetylation marks and tri-methylation of lysine 4. Distinct peaks of modified histones are found across the switch region, most notably at the 5' splice donor site of the germline (I) exon, which also accumulates AID. These data suggest that acetylation and K4 tri-methylation of histone H3 may represent marks of recombinationally active chromatin and further implicates splicing in the regulation of AID action.