[PDF][PDF] Instructive role of the transcription factor E2A in early B lymphopoiesis and germinal center B cell development

K Kwon, C Hutter, Q Sun, I Bilic, C Cobaleda, S Malin… - Immunity, 2008 - cell.com
K Kwon, C Hutter, Q Sun, I Bilic, C Cobaleda, S Malin, M Busslinger
Immunity, 2008cell.com
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 …
Summary
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.
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