The Journal of Experimental Medicine
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Published online 12 April 2004 doi:10.1084/jem.20031180
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 199, Number 8, 1101-1112
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Receptor Editing and Marginal Zone B Cell Development Are Regulated by the Helix-Loop-Helix Protein, E2A

Melanie W. Quong1, Annica Martensson2, Anton W. Langerak3, Richard R. Rivera1, David Nemazee2, and Cornelis Murre1

1 Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093
2 Division of Immunology, The Scripps Research Institute, La Jolla, CA 92037
3 Department of Immunology, Erasmus University, Rotterdam, 3000 DR, Netherlands

Address correspondence to Cornelis Murre, Div. of Biological Sciences, University of California, San Diego, La Jolla, CA 92093. Phone: (858) 534-8796; Fax: (858) 534-7550; email: murre{at}biomail.ucsd.edu

Previous studies have indicated that the E2A gene products are required to initiate B lineage development. Here, we demonstrate that E2A+/– B cells that express an autoreactive B cell receptor fail to mature due in part to an inability to activate secondary immunoglobulin (Ig) light chain gene rearrangement. Both RAG1/2 gene expression and RS deletion are severely defective in E2A+/– mice. Additionally, we demonstrate that E2A+/– mice show an increase in the proportion of marginal zone B cells with a concomitant decrease in the proportion of follicular B cells. In contrast, Id3-deficient splenocytes show a decline in the proportion of marginal zone B cells. Based on these observations, we propose that E-protein activity regulates secondary Ig gene rearrangement at the immature B cell stage and contributes to cell fate determination of marginal zone B cells. Additionally, we propose a model in which E-proteins enforce the developmental checkpoint at the immature B cell stage.

Key Words: E-proteins • Id3 • RAG • follicular B cells • checkpoint


Abbreviations used in this paper: BCR, B cell receptor; EBF, early B cell factor; GFP, green fluorescent protein; HEL, hen egg lysozyme; HSA, heat-stable antigen; IgH, Ig heavy chain; IgL, Ig light chain; RSS, recombination signal sequence.


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