Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 213, Issue 7, Pages 1201-1221Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20152002
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Funding
- Boehringer Ingelheim
- European Research Council from the European Union Seventh Framework Program [291740-LymphoControl]
- Austrian Industrial Research Promotion Agency
- German Research Foundation [WO 1972/1-1]
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E2A is an essential regulator of early B cell development. Here, we have demonstrated that E2A together with E2-2 controlled germinal center (GC) B cell and plasma cell development. As shown by the identification of regulated E2A, E2-2 target genes in activated B cells, these E-proteins directly activated genes with important functions in GC B cells and plasma cells by inducing and maintaining DNase I hypersensitive sites. Through binding to multiple enhancers in the Igh 3' regulatory region and Aicda locus, E-proteins regulated class switch recombination by inducing both Igh germline transcription and AID expression. By regulating 3' Igk and Igh enhancers and a distal element at the Prdm1 (Blimp1) locus, E-proteins contributed to Igk, Igh, and Prdm1 activation in plasmablasts. Together, these data identified E2A and E2-2 as central regulators of B cell immunity.
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