Corrective Recombination of Mouse Immunoglobulin Kappa Alleles in Abelson Murine Leukemia Virus-Transformed Pre-B Cells

Abstract

Previous characterization of mouse immunoglobulin κ gene rearrangement products cloned from murine plasmacytomas has indicated that two recombination events can take place on a single κ allele (R. M. Feddersen and B. G. Van Ness, Proc. Natl. Acad. Sci. USA 82:4792-4797, 1985; M. A. Shapiro and M. Weigert, J. Immunol. 139:3834-3839, 1987). To determine whether multiple recombinations on a single κ allele can contribute to the formation of productive V-J genes through corrective recombinations, we have examined several Abelson murine leukemia virus-transformed pre-B-cell clones which rearrange the κ locus during cell culture. Clonal cell lines which had rearranged one κ allele nonproductively while maintaining the other allele in the germ line configuration were grown, and secondary subclones, which subsequently expressed κ protein, were isolated and examined for further κ rearrangement. A full spectrum of rearrangement patterns was observed in this sequential cloning, including productive and nonproductive recombinations of the germ line allele and secondary recombinations of the nonproductive allele. The results show that corrective V-J recombinations, with displacement of the nonproductive κ gene, occur with a significant frequency (6 of 17 κ-producing subclones). Both deletion and maintenance of the primary (nonfunctional) V-J join, as a reciprocal product, were observed.