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Immunity. 2001 Oct;15(4):545-55.

PU.1/Spi-B regulation of c-rel is essential for mature B cell survival.

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Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.


PU.1(+/-)Spi-B(-/-) mice exhibit reduced numbers of immature and mature B lymphocytes, which exhibit severe defects in response to BCR-mediated stimulation and poor survival. We found that expression of c-rel, a member of the Rel/NF-kappa B family, is dramatically reduced in PU.1(+/-)Spi-B(-/-) splenic B cells. Analysis of the murine c-rel promoter identified three PU.1/Spi-B binding sites critical for c-rel promoter activity. Furthermore, reintroduction of Rel protein restored wild-type B cell numbers to mice reconstituted with PU.1(+/-)Spi-B(-/-) bone marrow. These findings are the first to demonstrate that a member of the Rel/NF-kappa B family is directly regulated by Ets proteins and dissect the molecular basis for the function of two Ets factors, PU.1 and Spi-B, in promoting B lymphocyte survival.

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