Surface IgM mediated regulation of RAG gene expression in E mu‐N‐myc B cell lines

Transgenic mice carrying either the c‐myc or N‐myc oncogene deregulated by the immunoglobulin heavy chain enhancer element (E mu) develop both pre‐B and B cell lymphomas (E mu‐c‐myc and E mu‐N‐myc lymphomas). We report here that B cell lines derived from these tumors, as well as a line derived from...

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Bibliographic Details
Published in:The EMBO journal 1992-07, Vol.11 (7), p.2727-2734
Main Authors: Ma, A., Fisher, P., Dildrop, R., Oltz, E., Rathbun, G., Achacoso, P., Stall, A., Alt, F.W.
Format: Article
Language:English
Subjects:
Animals
B-Lymphocytes - metabolism
Biochemistry & Molecular Biology
Biological and medical sciences
Blotting, Northern
Bone Marrow - metabolism
Bone Marrow Cells
Cell Biology
Cell Transformation, Viral
DNA Nucleotidyltransferases - metabolism
DNA-Binding Proteins
Down-Regulation
Enhancer Elements, Genetic
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Gene Expression Regulation
Genes, myc
Homeodomain Proteins
Immunobiology
Immunoglobulin M - metabolism
Life Sciences & Biomedicine
Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation
Lymphoma, B-Cell - genetics
Lymphoma, B-Cell - metabolism
Mice
Mice, Transgenic
Nucleic Acid Hybridization
Proteins - genetics
Retroviridae
Science & Technology
Tumor Cells, Cultured
VDJ Recombinases
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Summary:Transgenic mice carrying either the c‐myc or N‐myc oncogene deregulated by the immunoglobulin heavy chain enhancer element (E mu) develop both pre‐B and B cell lymphomas (E mu‐c‐myc and E mu‐N‐myc lymphomas). We report here that B cell lines derived from these tumors, as well as a line derived from v‐myc retroviral transformation, simultaneously express surface immunoglobulin (a hallmark of mature B cells) as well as a common subset of genes normally restricted to the pre‐B stage of development‐including the recombinase activating genes RAG‐1 and RAG‐2. Continued RAG‐1 and RAG‐2 expression in these lines is associated with VDJ recombinase activity detected with a VDJ recombination substrate. Cross‐linking of the surface immunoglobulin on these lines with an anti‐mu antibody leads to rapid, specific and reversible down‐regulation of RAG‐1 and RAG‐2 gene expression. We also find that a small but significant percentage of normal surface immunoglobulin bearing bone marrow B cells express the RAG‐1 gene. These findings are discussed in the context of their possible implications for the control of specific gene expression during the pre‐B to B cell transition.
ISSN:0261-4189
1460-2075
DOI:10.1002/j.1460-2075.1992.tb05338.x