title: Pro-B cells sense productive immunoglobulin heavy chain rearrangement irrespective of polypeptide production.
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.
authors.affiliation: Division of Molecular Immunology, Department of Internal Medicine III, Nikolaus-Fiebiger-Center of Molecular Medicine, Friedrich-Alexander-University Erlangen-Nürnberg, D-91054 Erlangen, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Lutz
authors.forename: Marinus R
authors.initials: MR
authors.lastname: Heideman
authors.forename: Edith
authors.initials: E
authors.lastname: Roth
authors.forename: Paul
authors.initials: P
authors.lastname: van den Berk
authors.forename: Werner
authors.initials: W
authors.lastname: Müller
authors.forename: Chander
authors.initials: C
authors.lastname: Raman
authors.forename: Matthias
authors.initials: M
authors.lastname: Wabl
authors.forename: Heinz
authors.initials: H
authors.lastname: Jacobs
authors.forename: Hans-Martin
authors.initials: HM
authors.lastname: Jäck
mesh_terms: D000483:Alleles; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D051379:Mice; D010452:Peptide Biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D022661:RNA, Untranslated / Q000235:genetics; D045567:VDJ Recombinases / Q000378:metabolism
chemical_list: D007143:Immunoglobulin Heavy Chains; D012333:RNA, Messenger; D022661:RNA, Untranslated; D045567:VDJ Recombinases