New insights into pre-BCR and BCR signalling with relevance to B cell malignancies

Nat Rev Immunol. 2013 Aug;13(8):578-91. doi: 10.1038/nri3487.


The B cell receptor (BCR) and its precursor (pre-BCR) control B cell homeostasis, differentiation and function. Moreover, aberrant pre-BCR and BCR signalling have a central role in B cell neoplasia; for example, enhanced positive signalling or disrupted negative signalling downstream of the pre-BCR promotes B cell acute lymphocytic leukaemia. The emerging distinctions between tonic and chronic active BCR signalling have contributed to the identification of oncogenic targets downstream of BCR signalling in mature B cell neoplasms. Indeed, the encouraging results of several ongoing clinical trials that target the activity of phosphoinositide 3-kinase δ-isoform (PI3Kδ), Bruton tyrosine kinase (BTK) or spleen tyrosine kinase (SYK) downstream of the BCR highlight the therapeutic potential of inhibiting BCR signalling.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Agammaglobulinaemia Tyrosine Kinase
  • Bone Marrow Cells / cytology
  • Cell Differentiation
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Leukemia, B-Cell / immunology
  • Leukemia, B-Cell / metabolism*
  • Lymphoma, B-Cell / immunology
  • Lymphoma, B-Cell / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / immunology
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / metabolism*
  • Protein-Tyrosine Kinases / metabolism
  • Receptors, Antigen, B-Cell / immunology
  • Receptors, Antigen, B-Cell / metabolism*
  • Signal Transduction
  • Syk Kinase


  • Intracellular Signaling Peptides and Proteins
  • Receptors, Antigen, B-Cell
  • Phosphatidylinositol 3-Kinases
  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase
  • BTK protein, human
  • SYK protein, human
  • Syk Kinase