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

Shawn P Fahl1, Rowena B Crittenden, David Allman

  • 1Department of Microbiology, University of Virginia Health System, Charlottesville, VA 22908, USA.

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The c-Myb transcription factor is essential for B cell development. Loss of c-Myb blocks B cell differentiation at the pro-B cell stage and impairs their survival, independent of IL-7 receptor signaling.

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Area of Science:

  • Immunology
  • Developmental Biology
  • Molecular Biology

Background:

  • The c-Myb transcription factor is vital for adult hematopoiesis.
  • Embryonic lethality of Myb-null mutations hinders study of c-Myb in lymphocyte development.

Purpose of the Study:

  • To investigate the role of c-Myb in early lymphocyte development, specifically B cell differentiation.
  • To elucidate the mechanisms by which c-Myb regulates B cell survival and differentiation.

Main Methods:

  • Tissue-specific inactivation of the Myb locus in early progenitor cells (Myb(f/f) Mb1-cre mice).
  • Analysis of B cell differentiation markers (CD19) and gene expression (IL-7 receptor alpha-chain/CD127, Ebf1).
  • Retroviral transduction and stromal cell culture assays.

Main Results:

  • c-Myb is essential for differentiation of CD19(+) B-lineage cells, with differentiation blocked at the pre-pro-B cell stage.
  • c-Myb regulates the intrinsic survival of CD19(+) pro-B cells and expression of CD127 and Ebf1.
  • c-Myb's role in pro-B cell survival is independent of CD127, and its absence can be partially rescued by exogenous Ebf1.
  • Forced c-Myb expression in progenitors promotes myeloid differentiation, highlighting its crucial role in B-lineage commitment.

Conclusions:

  • c-Myb is crucial for B cell differentiation to the CD19(+) pro-B cell stage and for the survival of these cells.
  • c-Myb regulates B cell development through pathways independent of CD127.
  • Proper c-Myb expression levels are critical for directing progenitor cells towards the B-lineage.