Coordinate Regulation of B Cell Differentiation by the Transcription Factors EBF and E2A

Immunity. 1999 Jul;11(1):21-31. doi: 10.1016/s1074-7613(00)80078-3.

Abstract

The transcription factors EBF and E2A are required at a similar step in early B cell differentiation. EBF and E2A synergistically upregulate transcription of endogenous B cell-specific genes in a non-B cell line. Here, we examine a genetic collaboration between these factors in regulating B lymphopoiesis. We find that Ebf+/- E2a+/- mice display a marked defect in pro-B cell differentiation at a stage later than observed in the single homozygous mutant mice. Pro-B cells from Ebf+/- E2a+/- mice show reduced expression of lymphoid-specific transcripts, including Pax5, Rag1, Rag2, and mb-1. We also show that EBF directly binds and activates the Pax5 promoter. Together, these data show collaboration between EBF and E2A and provide insight into the hierarchy of transcription factors that regulate B lymphocyte differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • B-Lymphocyte Subsets / metabolism
  • B-Lymphocyte Subsets / pathology
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / metabolism*
  • B-Lymphocytes / pathology
  • Bone Marrow Cells / pathology
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / physiology*
  • Enhancer Elements, Genetic / immunology
  • Epitopes, B-Lymphocyte / genetics
  • Epitopes, B-Lymphocyte / metabolism
  • Gene Expression Regulation / immunology
  • Genetic Carrier Screening
  • Helix-Loop-Helix Motifs / genetics
  • Helix-Loop-Helix Motifs / immunology*
  • Immunoglobulin lambda-Chains / genetics
  • Lymphopenia / genetics
  • Lymphopenia / immunology
  • Lymphopenia / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Molecular Sequence Data
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • PAX5 Transcription Factor
  • Promoter Regions, Genetic / immunology
  • Stem Cells / metabolism
  • Stem Cells / pathology
  • TCF Transcription Factors
  • Trans-Activators / biosynthesis
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Trans-Activators / physiology*
  • Transcription Factor 7-Like 1 Protein
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics
  • Transcription Factors / immunology*
  • Transcription Factors / metabolism

Substances

  • DNA-Binding Proteins
  • Ebf1 protein, mouse
  • Epitopes, B-Lymphocyte
  • Immunoglobulin lambda-Chains
  • Nuclear Proteins
  • PAX5 Transcription Factor
  • Pax5 protein, mouse
  • TCF Transcription Factors
  • Tcf7l1 protein, mouse
  • Trans-Activators
  • Transcription Factor 7-Like 1 Protein
  • Transcription Factors

Associated data

  • GENBANK/AF148961