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    block this user Werner Muller

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    Faculty of Life Science, University of Manchester, Manchester

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

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    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.

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    Description

    Title : Pro-B cells sense productive immunoglobulin heavy chain rearrangement irrespective of polypeptide production.
    Author(s) : Johannes Lutz, Marinus R Heideman, Edith Roth, Paul Van Den Berk, Werner Müller, Chander Raman, Matthias Wabl, Heinz Jacobs, Hans-Martin Jäck
    Abstract : 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.
    Subject : unspecified
    Area : Other
    Language : English
    Year : 2011

    Affiliations Faculty of Life Science, University of Manchester, Manchester
    Journal : Proceedings of the National Academy of Sciences of the United St
    Volume : 108
    Issue : 26
    Pages : 10644-10649
    Url : http://www.ncbi.nlm.nih.gov/pubmed/21670279

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    Werner's Peer Evaluation activity

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