c-Myb Is Critical for B Cell Development and Maintenance of Follicular B Cells

• Published in: Immunity (Cambridge, Mass.) Vol. 23; no. 3; pp. 275 - 286
• Main Authors: Thomas, Matthew D., Kremer, Christopher S., Ravichandran, Kodi S., Rajewsky, Klaus, Bender, Timothy P.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2005; Elsevier Limited
• Subjects: Animals; Apoptosis - immunology; B-Cell Activating Factor; B-Lymphocytes - cytology; B-Lymphocytes - immunology; Blotting, Northern; Blotting, Southern; Bone marrow; Bone Marrow - immunology; Cell cycle; Cell Proliferation; Colleges & universities; Flow Cytometry; Immune system; In Situ Nick-End Labeling; Lymphopoiesis - immunology; Membrane Proteins - immunology; Membrane Proteins - metabolism; Mice; Protein Kinase C - immunology; Protein Kinase C - metabolism; Proteins; Proto-Oncogene Proteins c-myb - genetics; Proto-Oncogene Proteins c-myb - immunology; Receptors, Tumor Necrosis Factor - immunology; Receptors, Tumor Necrosis Factor - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Rodents; Spleen - cytology; Spleen - immunology; Stem cells; Tumor Necrosis Factor-alpha - immunology; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2005.08.005

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.