The development of early and mature B cells is impaired in mice deficient for the Ets-1 transcription factor

Eur J Immunol. 2004 Nov;34(11):3187-96. doi: 10.1002/eji.200425352.


The Ets-1 transcription factor is essential for normal development of the natural killer and T cell lineages; however, its role in B cell development remains poorly understood. To address this issue, we used gene targeting to inactivate Ets-1 in mice (Ets-1(-/-)). We show here that the development of B cell precursors, particularly steps requiring pre-B cell receptor function, is defective in Ets-1(-/-) mice. Peripheral B cell subsets were analyzed in RAG2-deficient mice reconstituted with Ets-1(-/-) fetal liver cells. In such Ets-1(-/-) chimeric mice, B cell precursors develop into IgM/IgD-bearing cells, but B-1a cells as well as transitional-2 and marginal zone B cell subsets of the spleen are absent. In response to B cell receptor stimulation, Ets-1(-/-) splenic B cells fail to express the CD69 and CD25 activation markers. Furthermore, despite activation of ERK and JNK signaling pathways, Ets-1-deficient B cells do not proliferate and die following BCR engagement. These findings demonstrate that the effect of Ets-1 inactivation is not restricted to the terminal B cell differentiation stage, but also affects the development and function of earlier B cell subsets.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / immunology
  • B-Lymphocyte Subsets / cytology*
  • B-Lymphocyte Subsets / immunology
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / immunology
  • Cell Differentiation / immunology
  • Flow Cytometry
  • Immunoglobulin Heavy Chains / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Peritoneum / immunology
  • Proto-Oncogene Protein c-ets-1
  • Proto-Oncogene Proteins / deficiency*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / immunology
  • Proto-Oncogene Proteins c-ets
  • Receptors, Antigen, B-Cell / immunology
  • Recombination, Genetic / immunology
  • Spleen / immunology
  • Transcription Factors / deficiency*
  • Transcription Factors / genetics
  • Transcription Factors / immunology
  • Transcription, Genetic / immunology


  • Antigens, CD
  • Ets1 protein, mouse
  • Immunoglobulin Heavy Chains
  • Proto-Oncogene Protein c-ets-1
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ets
  • Receptors, Antigen, B-Cell
  • Transcription Factors