| First Author | Lutz J | Year | 2011 |
| Journal | Proc Natl Acad Sci U S A | Volume | 108 |
| Issue | 26 | Pages | 10644-9 |
| PubMed ID | 21670279 | Mgi Jnum | J:173549 |
| Mgi Id | MGI:5014441 | Doi | 10.1073/pnas.1019224108 |
| Citation | Lutz J, et al. (2011) Pro-B cells sense productive immunoglobulin heavy chain rearrangement irrespective of polypeptide production. Proc Natl Acad Sci U S A 108(26):10644-9 |
| abstractText | 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 muH mRNA that does not encode muH 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 muH mRNA may thus contribute to efficient H chain allelic exclusion. |
