7926759

pubmed:Citation

6

Lymphoid cells transformed by Abelson murine leukemia virus have provided one of the classic models for study of early B-cell development and immunoglobulin rearrangement. Most of these cells have rearranged their heavy-chain locus but not their light chain genes, suggesting that an active v-abl protein interferes with this differentiation step. To test this hypothesis, light-chain gene structure was examined in pre-B cells transformed by temperature-sensitive mutants of the Abelson virus and in derivatives that survive at the nonpermissive temperature because they express a human BCL-2 gene. Our studies reveal that inactivation of the v-abl protein tyrosine kinase triggers high-frequency rearrangement of kappa and lambda light-chain genes. These events are accompanied by marked increases in the expression of RAG-1 and RAG-2 RNAs. These increases occur in the absence of protein synthesis but are dependent on inactivation of the v-abl protein tyrosine kinase. As documented in the accompanying paper (Klug et al., this issue), an active v-abl protein also suppresses the activity of NF-kappa B/rel and expression controlled by the kappa intron enhancer. Together these data demonstrate that the v-abl protein specifically interferes with light-chain gene rearrangement by suppressing at least two pathways essential for this stage of B-cell differentiation and suggest that tyrosine phosphorylation is important in regulating RAG gene expression.

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688-97

pubmed-meshheading:7926759-Abelson murine leukemia virus, pubmed-meshheading:7926759-Animals, pubmed-meshheading:7926759-Base Sequence, pubmed-meshheading:7926759-Blotting, Western, pubmed-meshheading:7926759-Cell Line, Transformed, pubmed-meshheading:7926759-DNA Nucleotidyltransferases, pubmed-meshheading:7926759-DNA Primers, pubmed-meshheading:7926759-DNA-Binding Proteins, pubmed-meshheading:7926759-Enhancer Elements, Genetic, pubmed-meshheading:7926759-Gene Expression, pubmed-meshheading:7926759-Gene Rearrangement, pubmed-meshheading:7926759-Genes, Immunoglobulin, pubmed-meshheading:7926759-Homeodomain Proteins, pubmed-meshheading:7926759-Humans, pubmed-meshheading:7926759-Immunoglobulin Light Chains, pubmed-meshheading:7926759-Immunoglobulin kappa-Chains, pubmed-meshheading:7926759-Immunoglobulin lambda-Chains, pubmed-meshheading:7926759-Integrases, pubmed-meshheading:7926759-Introns, pubmed-meshheading:7926759-Lymphocytes, pubmed-meshheading:7926759-Mice, pubmed-meshheading:7926759-Molecular Sequence Data, pubmed-meshheading:7926759-NF-kappa B, pubmed-meshheading:7926759-Nuclear Proteins, pubmed-meshheading:7926759-Oncogene Proteins v-abl, pubmed-meshheading:7926759-Polymerase Chain Reaction, pubmed-meshheading:7926759-Protein Biosynthesis, pubmed-meshheading:7926759-Protein-Tyrosine Kinases, pubmed-meshheading:7926759-Proto-Oncogene Proteins, pubmed-meshheading:7926759-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:7926759-Proto-Oncogene Proteins c-rel, pubmed-meshheading:7926759-Recombinases

An active v-abl protein tyrosine kinase blocks immunoglobulin light-chain gene rearrangement.

Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't