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

EMBO J. 1992 Jul;11(7):2727-34. doi: 10.1002/j.1460-2075.1992.tb05338.x.

Abstract

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.

Publication types

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

MeSH terms

  • Animals
  • B-Lymphocytes / metabolism*
  • Blotting, Northern
  • Bone Marrow / metabolism
  • Bone Marrow Cells
  • Cell Transformation, Viral
  • DNA Nucleotidyltransferases / metabolism
  • DNA-Binding Proteins*
  • Down-Regulation
  • Enhancer Elements, Genetic
  • Gene Expression Regulation*
  • Genes, myc*
  • Homeodomain Proteins*
  • Immunoglobulin M / metabolism*
  • Lymphoma, B-Cell / genetics
  • Lymphoma, B-Cell / metabolism
  • Mice
  • Mice, Transgenic
  • Nucleic Acid Hybridization
  • Proteins / genetics*
  • Retroviridae
  • Tumor Cells, Cultured
  • VDJ Recombinases

Substances

  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Immunoglobulin M
  • Proteins
  • Rag2 protein, mouse
  • V(D)J recombination activating protein 2
  • RAG-1 protein
  • DNA Nucleotidyltransferases
  • VDJ Recombinases