Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 108, Issue 26, Pages 10644-10649Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1019224108
Keywords
-
Categories
Funding
- Interdisciplinary Center for Clinical Research
- Deutsche Forschungsgemeinschaft [SFB 466, FOR 832, JA 968/4]
- Netherlands Organization for Scientific Research
- Dutch Cancer Foundation [917.56.328, KWF 2008-4112]
- National Institutes of Health [R01AI041570]
Ask authors/readers for more resources
B-lymphocyte development is dictated by the protein products of functionally rearranged Ig heavy (H) and light (L) chain genes. Ig rearrangement begins in pro-B cells at the IgH locus. If pro-B cells generate a productive allele, they assemble a pre-B cell receptor complex, which signals their differentiation into pre-B cells and their clonal expansion. Pre-B cell receptor signals are also thought to contribute to allelic exclusion by preventing further IgH rearrangements. Here we show in two independent mouse models that the accumulation of a stabilized mu H mRNA that does not encode mu H chain protein specifically impairs pro-B cell differentiation and reduces the frequency of rearranged IgH genes in a dose-dependent manner. Because noncoding IgH mRNA is usually rapidly degraded by the nonsense-mediated mRNA decay machinery, we propose that the difference in mRNA stability allows pro-B cells to distinguish between productive and nonproductive Ig gene rearrangements and that mu H mRNA may thus contribute to efficient H chain allelic exclusion.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available