Abstract
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
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Animals
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Anticarcinogenic Agents / immunology
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B-Lymphocytes / cytology*
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B-Lymphocytes / immunology*
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Carrier Proteins / genetics
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Carrier Proteins / immunology*
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Cell Differentiation
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Cell Division
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Genes, Tumor Suppressor
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Hematopoietic Stem Cells / cytology
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Hematopoietic Stem Cells / immunology
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Lymphoma, B-Cell / etiology
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Lymphoma, B-Cell / genetics
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Lymphoma, B-Cell / immunology
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Mice
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Mice, Inbred BALB C
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Mice, Knockout
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Phosphoproteins / deficiency
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Phosphoproteins / genetics
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Phosphoproteins / immunology*
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Signal Transduction
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Splenomegaly / etiology
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Splenomegaly / genetics
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Splenomegaly / immunology
Substances
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Adaptor Proteins, Signal Transducing
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Anticarcinogenic Agents
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B cell linker protein
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Carrier Proteins
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Phosphoproteins