high resolution analysis of the chromatin landscape of the ige switch region in human b cells高分辨率的染色质景观分析ige开关地区人类的b细胞.pdfVIP

High Resolution Analysis of the Chromatin Landscape of the IgE Switch Region in Human B Cells 1 2,3,4 2,3,4 2,3,4 2,3,4 Sandeep Dayal , Jakub Nedbal , Philip Hobson , Alison M. Cooper , Hannah J. Gould , Martin 1 1 2,3 Gellert , Gary Felsenfeld *, David J. Fear * 1 Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, United States of America, 2 Division of Asthma, Allergy and Lung Biology, King’s College London, London, United Kingdom, 3 Medical Research Council and Asthma UK Centre in Allergic Mechanisms of Asthma, King’s College London, London, United Kingdom, 4 Randall Division of Cell and Molecular Biophysics, King’s College London, London, United Kingdom Abstract 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 nucl