The adaptor protein SLP-65 acts as a tumor suppressor that limits pre-B cell expansion.
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.
Flemming
Alexandra
A
Institute for Biology III, Albert-Ludwigs University of Freiburg and Max Planck Institute for Immunobiology, Stuebeweg 51, 79108 Freiburg, Germany.
Brummer
Tilman
T
Reth
Michael
M
Jumaa
Hassan
H
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D016588:Anticarcinogenic Agents / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D002454:Cell Differentiation; D002455:Cell Division; D016147:Genes, Tumor Suppressor; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000209:etiology / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010750:Phosphoproteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D013163:Splenomegaly / Q000209:etiology / Q000235:genetics / Q000276:immunology
D048868:Adaptor Proteins, Signal Transducing; D016588:Anticarcinogenic Agents; C113939:B cell linker protein; D002352:Carrier Proteins; D010750:Phosphoproteins