Instructive role of the transcription factor E2A in early B lymphopoiesis and germinal center B cell development.
The transcription factor E2A controls the initiation of B lymphopoiesis, which is arrested at the pre-pro-B cell stage in E2A-deficient mice. Here, we demonstrate by conditional mutagenesis that E2A is essential for the development of pro-B, pre-B, and immature B cells in the bone marrow. E2A is, however, dispensable for the generation of mature B cells and plasma cells in peripheral lymphoid organs. In contrast, germinal center B cell development is impaired in the absence of E2A despite normal AID expression and class-switch recombination. Molecular analysis revealed that E2A is required not only for initiating but also for maintaining the expression of Ebf1, Pax5, and the B cell gene program in pro-B cells. Notably, precocious Pax5 transcription from the Ikzf1 locus promotes pro-B cell development in E2A-deficient mice, demonstrating that ectopic Pax5 expression is sufficient to activate the B lymphoid transcription program in vivo in the absence of E2A.
Research Institute of Molecular Pathology, Vienna Biocenter, Dr. Bohr-Gasse 7, A-1030 Vienna, Austria.
Kyongrim
K
Kwon
Caroline
C
Hutter
Qiong
Q
Sun
Ivan
I
Bilic
César
C
Cobaleda
Stephen
S
Malin
Meinrad
M
Busslinger
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology; D002460:Cell Line; D002470:Cell Survival; D018858:Germinal Center / Q000276:immunology* / Q000378:metabolism; D051740:Ikaros Transcription Factor / Q000235:genetics / Q000378:metabolism*; D054503:Lymphoid Progenitor Cells / Q000166:cytology* / Q000378:metabolism; D038041:Lymphopoiesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D016296:Mutagenesis; D051757:PAX5 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D051740:Ikaros Transcription Factor; D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse; C075668:Tcf3 protein, mouse