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E2A promotes the survival of precursor and mature B lymphocytes.

Publication ,  Journal Article
Lazorchak, AS; Wojciechowski, J; Dai, M; Zhuang, Y
Published in: J Immunol
August 15, 2006

The basic helix-loop-helix transcription factor E2A is an essential regulator of B lymphocyte lineage commitment and is required to activate the expression of numerous B lineage-specific genes. Studies involving ectopic expression of Id proteins, which inhibit E2A as well as other basic helix-loop-helix proteins such as HEB, suggest additional roles of E2A at later stages of B cell development. We use E2A-deficient and E2A and HEB double-deficient pre-B cell lines to directly assess the function of E2A and HEB in B cell development after lineage commitment. We show that, in contrast to the established role of E2A in lineage commitment, elimination of E2A and HEB in pre-B cell lines has only a modest negative impact on B lineage gene expression. However, E2A single and E2A and HEB double-deficient but not HEB single-deficient cell lines show dramatically enhanced apoptosis upon growth arrest. To address the possible role of E2A in the regulation of B cell survival in vivo, we crossed IFN-inducible Cre-transgenic mice to E2A conditional mice. Cre-mediated E2A deletion resulted in a block in bone marrow B cell development and a significant reduction in the proportion and total number of splenic B cells in these mice. We show that Cre-mediated deletion of E2A in adoptively transferred mature B cells results in the rapid depletion of the transferred population within 24 h of Cre induction. These results reveal that E2A is not required to maintain B cell fate but is essential in promoting pre-B and B cell survival.

Duke Scholars

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

August 15, 2006

Volume

177

Issue

4

Start / End Page

2495 / 2504

Location

United States

Related Subject Headings

  • Mice, Transgenic
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Immunology
  • Hematopoietic Stem Cells
  • Gene Expression Regulation, Developmental
  • Cell Survival
  • Cell Lineage
  • Cell Line
 

Citation

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MLA
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Lazorchak, A. S., Wojciechowski, J., Dai, M., & Zhuang, Y. (2006). E2A promotes the survival of precursor and mature B lymphocytes. J Immunol, 177(4), 2495–2504. https://doi.org/10.4049/jimmunol.177.4.2495
Lazorchak, Adam S., Jason Wojciechowski, Meifang Dai, and Yuan Zhuang. “E2A promotes the survival of precursor and mature B lymphocytes.J Immunol 177, no. 4 (August 15, 2006): 2495–2504. https://doi.org/10.4049/jimmunol.177.4.2495.
Lazorchak AS, Wojciechowski J, Dai M, Zhuang Y. E2A promotes the survival of precursor and mature B lymphocytes. J Immunol. 2006 Aug 15;177(4):2495–504.
Lazorchak, Adam S., et al. “E2A promotes the survival of precursor and mature B lymphocytes.J Immunol, vol. 177, no. 4, Aug. 2006, pp. 2495–504. Pubmed, doi:10.4049/jimmunol.177.4.2495.
Lazorchak AS, Wojciechowski J, Dai M, Zhuang Y. E2A promotes the survival of precursor and mature B lymphocytes. J Immunol. 2006 Aug 15;177(4):2495–2504.

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

August 15, 2006

Volume

177

Issue

4

Start / End Page

2495 / 2504

Location

United States

Related Subject Headings

  • Mice, Transgenic
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Immunology
  • Hematopoietic Stem Cells
  • Gene Expression Regulation, Developmental
  • Cell Survival
  • Cell Lineage
  • Cell Line