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

Transgenic mice carrying either the c-myc or N-myc oncogene deregulated by the immunoglobulin heavy chain enhancer element (Eμ) develop both pre-B and B cell lymphomas (Eμ-c-myc and Eμ-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-μ antibody leads to rapid, specific and reversible down-regulation of RAG-I 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-I 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.