Molecular functions of the transcription factors E2A and E2-2 in controlling germinal center B cell and plasma cell development

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 acti...

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Veröffentlicht in:The Journal of experimental medicine 2016-06, Vol.213 (7), p.1201-1221
Hauptverfasser: Wöhner, Miriam, Tagoh, Hiromi, Bilic, Ivan, Jaritz, Markus, Poliakova, Daniela Kostanova, Fischer, Maria, Busslinger, Meinrad
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Sprache:eng
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Zusammenfassung: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.
ISSN:0022-1007
1540-9538
DOI:10.1084/jem.20152002