E2A Proteins Are Required for Proper B Cell Development and Initiation of Immunoglobulin Gene Rearrangements

Cell. 1994 Dec 2;79(5):885-92. doi: 10.1016/0092-8674(94)90077-9.

Abstract

E12 and E47 are two helix-loop-helix transcription factors that arise by alternative splicing of the E2A gene. Both have been implicated in the regulation of immunoglobulin gene expression. We have now generated E2A (-/-) mice by gene targeting. E2A-null mutant mice fail to generate mature B cells. The arrest of B cell development occurs at an early stage, since no immunoglobulin DJ rearrangements can be detected in homozygous mutant mice. While immunoglobulin germline I mu RAG-1, mb-1, CD19, and lambda 5 transcripts are dramatically reduced in fetal livers of E2A (-/-) mice, B29 and mu degrees transcripts are present, but at lower levels. In addition, we show that Pax-5 transcripts are significantly reduced in fetal livers of E2A (-/-) mice. These data suggest a crucial role for E2A products as central regulators in early B cell differentiation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • B-Lymphocytes / physiology*
  • Base Sequence
  • Cell Differentiation
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Rearrangement
  • Genes, Immunoglobulin / genetics*
  • Homeodomain Proteins*
  • Homozygote
  • Immunoglobulin lambda-Chains / genetics
  • Lymphoid Tissue / immunology
  • Mice
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Proteins / genetics
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • TCF Transcription Factors
  • Transcription Factor 7-Like 1 Protein
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Immunoglobulin lambda-Chains
  • Proteins
  • RNA, Messenger
  • TCF Transcription Factors
  • Tcf7l1 protein, mouse
  • Transcription Factor 7-Like 1 Protein
  • Transcription Factors
  • RAG-1 protein