Regulation of B-cell proliferation and differentiation by pre-B-cell receptor signalling

Nat Rev Immunol. 2009 Mar;9(3):195-205. doi: 10.1038/nri2491.


The pre-B-cell receptor (pre-BCR) is expressed following the productive recombination of the immunoglobulin heavy chain gene. Signals through the pre-BCR are required for initiating diverse processes in pre-B cells, including proliferation and recombination of the light chain gene, which eventually lead to the differentiation of pre-B cells to immature B cells. However, the molecular mechanisms by which the pre-BCR promotes these processes remain largely unresolved. Recent findings suggest that forkhead box O (FOXO) transcription factors connect pre-BCR signalling to the activation of the recombination machinery. In this Review, we discuss how FOXO transcription factors are regulated by the pre-BCR to allow the progression of the cell cycle and the recombination of the light chain gene.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • Cell Division
  • Forkhead Transcription Factors / metabolism*
  • Humans
  • Immunoglobulin Light Chains / genetics*
  • Lymphopoiesis / immunology*
  • Pre-B Cell Receptors / metabolism*
  • Recombination, Genetic
  • Signal Transduction


  • Forkhead Transcription Factors
  • Immunoglobulin Light Chains
  • Pre-B Cell Receptors