C-Myb Is critical for B cell development and maintenance of follicular B cells

Matthew D. Thomas, Christopher S. Kremer, Kodi S. Ravichandran, Klaus Rajewsky, Timothy P. Bender

Research output: Contribution to journalArticlepeer-review

143 Scopus citations

Abstract

The c-Myb transcription factor is crucial during definitive hematopoiesis. However, the embryonic lethality of Myb traditional null mutations has precluded analysis of c-Myb function in lymphocytes. Using tissue-specific inactivation at the Myb locus, we demonstrate that loss of Myb causes a partial block during B cell development at the pro-B to pre-B cell transition, resulting in greatly decreased output of new B cells from the bone marrow. Furthermore, we demonstrate that Myb is not essential for the proliferation of splenic B cells, but that loss of c-Myb function prevents normal B cell homeostasis due to decreased splenic B cell survival. Decreased survival is accompanied by hyporesponsiveness to the B cell survival factor BLyS (also termed BAFF), decreased expression of the BLyS receptor 3 (BR3), and altered regulation of PKCδ nuclear accumulation. Thus, c-Myb is important during multiple stages of B-lymphopoiesis.

Original languageEnglish
Pages (from-to)275-286
Number of pages12
JournalImmunity
Volume23
Issue number3
DOIs
StatePublished - Sep 2005

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