E2A proteins are required for proper B cell development and initiation of immunoglobulin gene rearrangements

doi:10.1016/0092-8674(94)90077-9

Cell

Volume 79, Issue 5, 2 December 1994, Pages 885-892

https://doi.org/10.1016/0092-8674(94)90077-9 Get rights and content

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_μ RAG-1, mb-1, CD19, and λ5 transcripts are dramatically reduced in fetal livers of E2A (−/−) mice, B29 and μ° 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.

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Cell

ArticleE2A proteins are required for proper B cell development and initiation of immunoglobulin gene rearrangements

Abstract

Cell

Cell

Cell

Cell

Cell

Cell

Cell

Biochim. Biophys. Acta

Cell

Cell

Dev. Biol.

Cell

Pax-5 encodes the transcription factor BSAP and is expressed in B lymphocytes, developing CNS, and adult testis

Genes Dev.

Coordination of immunoglobulin DJH transcription and D-to-JH rearrangement by promoter-enhancer approximation

Mol. Cell. Biol.

Development of the primary antibody repertoire

Science

Distribution and characterization of helix-loop-helix enhancer-binding proteins from pancreatic beta-cells and lymphocytes

Nucl. Acids Res.

E2A and E2-2 are subunits of B-cell-specific E2-box DNA-binding proteins

Mol. Cell. Biol.

A novel B-cell lineage-specific transcription factor present at early but not late stages of differentiation

Genes Dev.

Mutations of the intronic IgH enhancer and its flanking sequences differentially affect accessibility of the JH locus

EMBO J.

Cell type specific contacts to immunoglobulin enhancers in nuclei

Nature

B-lineage-specific interactions of an immunoglobulin enhancer with cellular factors in vivo

Science

Predominance of the prototypic T15 anti-phosphorylcholine junctional sequence in neonatal pre-B cells

J. Immunol.

Lack of N regions in fetal and neonatal mouse immunoglobulin V-d-J junctional sequences

J. Exp. Med.

Predominance of VH-D-JH junctions occuring at sites of short sequence homology results in limited junctional diversity in neonatal antibodies

J. Immunol.

Separate elements control DJ and VDJ rearrangement in a transgenic recombination substrate

EMBO J.

Resolution and characterization of pro-B and pre- pro-B cell stages in normal mouse bone marrow

J. Exp. Med.

Article
E2A proteins are required for proper B cell development and initiation of immunoglobulin gene rearrangements

Coordination of immunoglobulin DJ_H transcription and D-to-J_H rearrangement by promoter-enhancer approximation

Mutations of the intronic IgH enhancer and its flanking sequences differentially affect accessibility of the J_H locus

Predominance of V_H-D-J_H junctions occuring at sites of short sequence homology results in limited junctional diversity in neonatal antibodies