Assessing the pathogenic potential of the V(D)J recombinase by interlocus immunoglobulin light-chain gene rearrangement.

Molecular and Cellular Biology
S N Bailey, N Rosenberg

Abstract

Chromosomal translocations involving antigen receptor genes and oncogenes have been observed in several forms of lymphoid malignancy. Observations of their lymphocyte-restricted occurrence and a molecular analysis of some translocation breakpoints have suggested that some of these rearrangements are generated by V(D)J recombinase activity. However, a direct correlation between this activity and the generation of such rearrangements has never been established. In addition, because these aberrant rearrangements are usually detected only after a tumor has been formed, the frequency with which the recombinase machinery generates translocations has never been assessed directly. To approach these issues, immunoglobulin light-chain gene rearrangements were induced in pre-B cells transformed by temperature-sensitive mutants of Abelson murine leukemia virus and PCR was used to identify interlocus recombinants. Vlambda Jkappa and Vkappa Jlambda rearrangements as well as signal joints resulting from the recombination of Vlambda and Jkappa coding elements were recovered and were found to be similar in structure to conventional intrachromosomal joints. Because these products were detected only when the cells were undergoing active intralocu...Continue Reading

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Citations

Jan 10, 2002·The Journal of Experimental Medicine·Rodrig MarculescuBertrand Nadel
Jun 5, 2002·Annual Review of Biochemistry·Martin Gellert
Sep 17, 2003·Nature Reviews. Immunology·David B Roth
Mar 18, 2000·The Journal of Biological Chemistry·A Tevelev, D G Schatz
Jul 9, 2003·Immunological Reviews·Kevin D MillsFrederick W Alt
Jun 22, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·H H BendallE M Oltz
Jun 1, 1997·Molecular and Cellular Biology·S M LewisL Czyzyk

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