c-Myb is required for pro-B cell differentiation.

Abstract

The c-Myb transcription factor is required for normal adult hematopoiesis. However, the embryonic lethality of Myb-null mutations has been an impediment to identifying roles for c-Myb during lymphocyte development. We have used tissue-specific inactivation of the Myb locus in early progenitor cells to demonstrate that c-Myb is absolutely required for the differentiation of CD19(+) B-lineage cells and B cell differentiation is profoundly blocked beyond the pre-pro-B cell stage in Myb(f/f) Mb1-cre mice. We demonstrate that c-Myb is required for the intrinsic survival of CD19(+) pro-B cells as well as the proper expression of the alpha-chain of the IL-7 receptor (CD127) and Ebf1. However, survival of c-Myb-deficient CD19(+) pro-B cells cannot be rescued by transduction with CD127-producing retrovirus, suggesting that c-Myb controls a survival pathway independent of CD127. Furthermore, c-Myb-deficient progenitor cells inefficiently generate CD19(+) B-lineage cells during stromal cell culture but this process can be partially rescued with exogenous Ebf1. Thus, c-Myb does not appear to be required for commitment to B cell differentiation but is crucial for B cell differentiation to the CD19(+) pro-B cell stage as well as survival of CD19(+) pro-B cells. Surprisingly, forced c-Myb expression in lymphoid-primed multipotent progenitors favors differentiation toward the myeloid lineage, suggesting that proper c-Myb expression is crucial for B-lineage development.

DOI: 10.4049/jimmunol.0901187

9 Figures and Tables

Statistics

0204020102011201220132014201520162017
Citations per Year

79 Citations

Semantic Scholar estimates that this publication has 79 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Fahl2009cMybIR, title={c-Myb is required for pro-B cell differentiation.}, author={Shawn P . Fahl and Rowena B. Crittenden and David M. Allman and Timothy P. Bender}, journal={Journal of immunology}, year={2009}, volume={183 9}, pages={5582-92} }