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

Academic Article

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

    Digital Object Identifier (doi)

    Author List

  • Lutz J; Heideman MR; Roth E; Van Den Berk P; Müller W; Raman C; Wabl M; Jacobs H; Jäck HM
  • Start Page

  • 10644
  • End Page

  • 10649
  • Volume

  • 108
  • Issue

  • 26