Instructive role of the transcription factor E2A in early B lymphopoiesis and germinal center B cell development

Immunity. 2008 Jun;28(6):751-62. doi: 10.1016/j.immuni.2008.04.014.


The transcription factor E2A controls the initiation of B lymphopoiesis, which is arrested at the pre-pro-B cell stage in E2A-deficient mice. Here, we demonstrate by conditional mutagenesis that E2A is essential for the development of pro-B, pre-B, and immature B cells in the bone marrow. E2A is, however, dispensable for the generation of mature B cells and plasma cells in peripheral lymphoid organs. In contrast, germinal center B cell development is impaired in the absence of E2A despite normal AID expression and class-switch recombination. Molecular analysis revealed that E2A is required not only for initiating but also for maintaining the expression of Ebf1, Pax5, and the B cell gene program in pro-B cells. Notably, precocious Pax5 transcription from the Ikzf1 locus promotes pro-B cell development in E2A-deficient mice, demonstrating that ectopic Pax5 expression is sufficient to activate the B lymphoid transcription program in vivo in the absence of E2A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Bone Marrow Cells / cytology
  • Cell Line
  • Cell Survival
  • Germinal Center / immunology*
  • Germinal Center / metabolism
  • Ikaros Transcription Factor / genetics
  • Ikaros Transcription Factor / metabolism*
  • Lymphoid Progenitor Cells / cytology*
  • Lymphoid Progenitor Cells / metabolism
  • Lymphopoiesis* / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Mutagenesis
  • PAX5 Transcription Factor / genetics
  • PAX5 Transcription Factor / metabolism*
  • Plasma Cells / cytology
  • Plasma Cells / immunology
  • Plasma Cells / metabolism


  • Basic Helix-Loop-Helix Transcription Factors
  • PAX5 Transcription Factor
  • Pax5 protein, mouse
  • Tcf3 protein, mouse
  • Ikaros Transcription Factor