The adaptor protein SLP-65 acts as a tumor suppressor that limits pre-B cell expansion

Nat Immunol. 2003 Jan;4(1):38-43. doi: 10.1038/ni862. Epub 2002 Nov 18.


Mice deficient in the adaptor protein SLP-65 (also known as BLNK) have reduced numbers of mature B cells, but an increased pre-B cell compartment. We show here that compared to wild-type cells, SLP-65(-/-) pre-B cells show an enhanced ex vivo proliferative capacity. This proliferation requires interleukin 7 and expression of the pre-B cell receptor (pre-BCR). In addition, SLP-65(-/-) mice have a high incidence of pre-B cell lymphoma. Reintroduction of SLP-65 into SLP-65(-/-) pre-B cells led to pre-BCR down-regulation and enhanced differentiation. Our results indicate that SLP-65 regulates a developmental program that promotes differentiation and limits pre-B cell expansion, thereby acting as a tumor suppressor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Anticarcinogenic Agents / immunology
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / immunology*
  • Carrier Proteins / genetics
  • Carrier Proteins / immunology*
  • Cell Differentiation
  • Cell Division
  • Genes, Tumor Suppressor
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / immunology
  • Lymphoma, B-Cell / etiology
  • Lymphoma, B-Cell / genetics
  • Lymphoma, B-Cell / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Phosphoproteins / deficiency
  • Phosphoproteins / genetics
  • Phosphoproteins / immunology*
  • Signal Transduction
  • Splenomegaly / etiology
  • Splenomegaly / genetics
  • Splenomegaly / immunology


  • Adaptor Proteins, Signal Transducing
  • Anticarcinogenic Agents
  • B cell linker protein
  • Carrier Proteins
  • Phosphoproteins