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

G Bain, ECR Maandag, DJ Izon, D Amsen… - Cell, 1994 - cell.com
G Bain, ECR Maandag, DJ Izon, D Amsen, AM Kruisbeek, BC Weintraub, I Krop…
Cell, 1994cell.com
El2 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 (-I--) mice by gene targeting. ESA-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, RAG-I, mb-f, CD19, and 15 transcripts are …
Summary
El2 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 (-I--) mice by gene targeting. ESA-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, RAG-I, mb-f, CD19, and 15 transcripts are dramatically reduced in fetal livers of E2A (--I-) mice, 829 and pa transcripts are present, but at lower levels. In addition, we show that Pax-5 transcripts are significantly reduced in fetal livers of E2A (-I-) mice. These data suggest a crucial role for E2A products as central regulators in early B cell differentiation.
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