Naslov
Instructive Role of the Transcription Factor E2A in Early B Lymphopoiesis and Germinal Center B Cell Development

Autori
Kwon, Kyongrim ; Hutter, Caroline ; Qiong, Sun ; Bilić, Ivan ; Cobaleda César ; Malin, Stephen ; Busslinger, Meinrad

Izvornik
Immunity (1074-7613) 28 (2008), 6; 751-762

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
transcription factors ; lymphocytes

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne tehničke znanosti, Temeljne medicinske znanosti

POVEZANOST RADA