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 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.
Research Institute of Molecular Pathology, Vienna Biocenter, A-1030 Vienna, Austria.
Miriam
M
Wöhner
Research Institute of Molecular Pathology, Vienna Biocenter, A-1030 Vienna, Austria.
Hiromi
H
Tagoh
Research Institute of Molecular Pathology, Vienna Biocenter, A-1030 Vienna, Austria.
Ivan
I
Bilic
Research Institute of Molecular Pathology, Vienna Biocenter, A-1030 Vienna, Austria.
Markus
M
Jaritz
Research Institute of Molecular Pathology, Vienna Biocenter, A-1030 Vienna, Austria.
Daniela Kostanova
DK
Poliakova
Research Institute of Molecular Pathology, Vienna Biocenter, A-1030 Vienna, Austria.
Maria
M
Fischer
Research Institute of Molecular Pathology, Vienna Biocenter, A-1030 Vienna, Austria busslinger@imp.ac.at.
Meinrad
M
Busslinger
D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000276:immunology*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000276:immunology*; D003564:Cytidine Deaminase / Q000235:genetics / Q000276:immunology; D004742:Enhancer Elements, Genetic / Q000276:immunology; D018858:Germinal Center / Q000166:cytology / Q000276:immunology*; D017578:Immunoglobulin Class Switching / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology*; D000073940:Transcription Factor 4; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D003564:Cytidine Deaminase; D000073940:Transcription Factor 4; D000098830:AICDA (Activation-Induced Cytidine Deaminase); C075668:Tcf3 protein, mouse; C090743:Tcf4 protein, mouse