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

Cheng Jun Hu, Sridhar Rao, Diana L. Ramirez-Bergeron, Lee Ann Garrett-Sinha, Steve Gerondakis, Marcus R. Clark, M. Celeste Simon

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40 Citations (Scopus)

Abstract

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-κB 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-κB 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.

Original languageEnglish
Pages (from-to)545-555
Number of pages11
JournalImmunity
Volume15
Issue number4
DOIs
Publication statusPublished - 1 Jan 2001
Externally publishedYes

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