Broad feedback inhibition of pre-B-cell receptor signaling components

Jannek Hauser, Jiyoti Verma-Gaur, Thomas Grundström

Research output: Contribution to journalArticleResearchpeer-review

5 Citations (Scopus)

Abstract

During B lymphocyte development, first immunoglobulin heavy chain gene segments and then immunoglobulin light chain gene segments are rearranged to create antibody diversity. Early in the development, expression of a pre-B-cell receptor (pre-BCR) that has membrane-bound Ig heavy chain protein associated with surrogate light chain (SLC) proteins serves as a critical checkpoint that monitors for functional heavy chain rearrangement. Signaling from the pre-BCR induces survival and clonal expansion to select cells with good heavy chains, but it also down-regulates transcription of the genes for the SLC proteins and CD19 and limits its own proliferative signaling. Here we have analyzed whether the down-regulation is limited to the SLC proteins and CD19, and we show that the pre-BCR of primary mouse pre-B-cells instead is subject to a broad feedback inhibition of pre-BCR signaling components. Activation of signaling leads to down-regulation of the receptor proteins, many co-receptors and proteins participating in signal pathways from the receptor. Thus the down-regulation of the pre-BCR is much broader than previously assumed. We also show that Ca2+/calmodulin inhibition of the transcription factor E2A is required for the feedback inhibition of the pre-BCR signaling proteins.

Original languageEnglish
Pages (from-to)247-253
Number of pages7
JournalMolecular Immunology
Volume54
Issue number3-4
DOIs
Publication statusPublished - Jul 2013
Externally publishedYes

Keywords

  • Calcium signaling
  • Calmodulin
  • Cell proliferation
  • E2A
  • Gene regulation
  • Pre-BCR
  • Signal transduction

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