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 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.
Ma
A
A
Howard Hughes Medical Institute, Boston, MA.
Fisher
P
P
Dildrop
R
R
Oltz
E
E
Rathbun
G
G
Achacoso
P
P
Stall
A
A
Alt
F W
FW
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D015152:Blotting, Northern; D001853:Bone Marrow / Q000378:metabolism; D001854:Bone Marrow Cells; D002472:Cell Transformation, Viral; D004254:DNA Nucleotidyltransferases / Q000378:metabolism; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D016259:Genes, myc; D018398:Homeodomain Proteins; D007075:Immunoglobulin M / Q000378:metabolism*; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009693:Nucleic Acid Hybridization; D011506:Proteins / Q000235:genetics*; D012190:Retroviridae; D014407:Tumor Cells, Cultured; D045567:VDJ Recombinases
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D007075:Immunoglobulin M; D011506:Proteins; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases