TY - JOUR
T1 - C-Myb Is critical for B cell development and maintenance of follicular B cells
AU - Thomas, Matthew D.
AU - Kremer, Christopher S.
AU - Ravichandran, Kodi S.
AU - Rajewsky, Klaus
AU - Bender, Timothy P.
N1 - Funding Information:
The authors thank C. Goettlinger (University of Cologne) and Joanne Lannigan (University of Virginia) for help with cell sorting. This work was supported in part by grants AI43425 (NIH) to K.S.R., SFB 243 (Deutsche Forschungsgemeinschaft) to K.R., and CA85842 (NIH) and AI59294 (NIH) to T.P.B.
PY - 2005/9
Y1 - 2005/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=24944538805&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2005.08.005
DO - 10.1016/j.immuni.2005.08.005
M3 - Article
C2 - 16169500
AN - SCOPUS:24944538805
VL - 23
SP - 275
EP - 286
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 3
ER -