c-Myb is critical for B cell development and maintenance of follicular B cells.
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 PKCdelta nuclear accumulation. Thus, c-Myb is important during multiple stages of B-lymphopoiesis.
Thomas
Matthew D
MD
Department of Microbiology, P.O. Box 800734, University of Virginia Health System, Charlottesville, VA 22908, USA.
Kremer
Christopher S
CS
Ravichandran
Kodi S
KS
Rajewsky
Klaus
K
Bender
Timothy P
TP
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D053264:B-Cell Activating Factor; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D015152:Blotting, Northern; D015139:Blotting, Southern; D001853:Bone Marrow / Q000276:immunology; D049109:Cell Proliferation; D005434:Flow Cytometry; D020287:In Situ Nick-End Labeling; D038041:Lymphopoiesis / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D011493:Protein Kinase C / Q000276:immunology / Q000378:metabolism; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics / Q000276:immunology*; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
D053264:B-Cell Activating Factor; C120197:BLyS receptor; D008565:Membrane Proteins; D020598:Proto-Oncogene Proteins c-myb; D018124:Receptors, Tumor Necrosis Factor; C505720:Tnfsf13b protein, mouse; D014409:Tumor Necrosis Factor-alpha; D011493:Protein Kinase C