Critical roles for c-Myb in lymphoid priming and early B-cell development

Kylie T. Greig, Carolyn A. de Graaf, James M. Murphy, Marina R. Carpinelli, Swee Heng Milon Pang, Jon Frampton, Benjamin T. Kile, Douglas J. Hilton, Stephen L. Nutt

Research output: Contribution to journalArticleResearchpeer-review

46 Citations (Scopus)

Abstract

c-Myb is a transcription factor with functions in many hematopoietic lineages. c-Myb-deficient mice display reduced. numbers of B cells; however, it is unknown what role c-Myb plays in B lymphopoiesis because no critical target genes have been identified in the B-cell lineage. We demonstrate that conditional deletion of c-Myb in B-cell progenitors completely abolishes B-cell development. c-Myb is required for lymphoid progenitors to respond to the cytokines interleukin-7 and thymic stromal lymphopoietin; in the absence of sufficient c-Myb activity, mice display a B lymphopenia that closely resembles that observed in interleukin-7 receptor a-deficient animals. Analysis of the multipotent progenitor compartment indicates that c-Myb is also required for up-regulation of multiple lymphoid-associated genes, including Il7r, and for the subsequent development of the common lymphoid progenitor population. These data show that c-Myb plays a critical role in the regulatory pathways governing lymphoid specification and early B-cell differentiation.
Original languageEnglish
Pages (from-to)2796 - 2805
Number of pages10
JournalBlood
Volume115
Issue number14
DOIs
Publication statusPublished - 8 Apr 2010

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