volume 9 Number 51981 Nucleic Acids Research Misalignment of V and J gene segments resulting in a nonfunctional immunoglobuUn gene

The myeloma variant NS-ln has lost the functional immunogiobulin kappa gene which is present in i t s parent, myeloma MOPC-21. The variant retains a nonfunctional rearranged gene, M.21N, which undergoes RNA t ranscr ip t ion and processing to y ie ld a mature size ranRNA. This KRNA, however, is not translated into kappa polypeptide chains. The nonfunctional gene was cloned into Charon 4A to determine the basis for i t s i n a c t i v i t y. Nucleotide sequence analysis of a DNA fragment overlapping the V-J recombination s i te in the M.21N gene indicated that a misalignment had taken place during somatic recombination. This misalignment resul ts in a delet ion of four nucleotides at the 31 end of the V gene and, thus, a t ranslat ional reading frame s h i f t. In other respects the M.21N V gene, which corresponds to a d i f fe ren t VK subgroup than the functional gene of MOPC-21, appears normal