Pro-B cells sense productive immunoglobulin heavy chain rearrangement irrespective of polypeptide production

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 diffe...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS Jg. 108; H. 26; S. 10644
Hauptverfasser: Lutz, Johannes, Heideman, Marinus R, Roth, Edith, van den Berk, Paul, Müller, Werner, Raman, Chander, Wabl, Matthias, Jacobs, Heinz, Jäck, Hans-Martin
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 28.06.2011
Schlagworte:
Alleles
Animals
B-Lymphocytes - immunology
Immunoglobulin Heavy Chains - genetics
Mice
Peptide Biosynthesis
RNA, Messenger - genetics
RNA, Untranslated - genetics
VDJ Recombinases - metabolism
ISSN:1091-6490, 1091-6490
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Zusammenfassung: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 μH mRNA that does not encode μH 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 μH mRNA may thus contribute to efficient H chain allelic exclusion.
Bibliographie:ObjectType-Article-1
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ISSN:1091-6490
1091-6490
DOI:10.1073/pnas.1019224108