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Nucleic Acids Research, 1981, Vol. 9, No. 5 1101-1109
© 1981

MOLECULAR BIOLOGY

Misalignment of V and J gene segments resulting in a nonfunctional immunoglobulin gene

Alan Walfield**, Erik Selsing, Benjamin Arp and Ursula Storb*

Department of Microbiology and Immunology, University of Washington Seattle, WA 98195, USA

* To whom reprint requests should be sent.

Received December 18, 1980.

The myeloma variant NS-1n has lost the functional immunoglobulin kappa gene which is present in its parent, myeloma MOPC-21. The variant retains a nonfunctional rearranged gene, M.21N, which undergoes RNA transcription and processing to yield a mature size kmRNA. This kRNA, however, is not translated into kappa polypeptide chains. The nonfunctional gene was cloned into Charon 4A to determine the basis for its inactivity. Nucleotide sequence analysis of a DNA fragment overlapping the V-J recombination site in the M.21N gene indicated that a misalignment had taken place during somatic recombination. This misalignment results in a deletion of four nucleotides at the 3' end of the V gene and, thus, a translational reading frame shift. In other respects the M.21N V gene, which corresponds to a different VK subgroup than the functional gene of MOPC-21, appears normal.

** Present address: Department of Medicine, UCLA, Los Angeles, CA 90024


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