Comparison of different rearranged immunoglobulin kappa genes of a myeloma by electronmicroscopy and restriction mapping of cloned DNA: implications for "allelic exclusion".

We have studied the organization and function of different rearranged kappa genes in a myeloma, MOPC-21. Two kappa genes were cloned into Charon 4A and compared with each other and with a cloned germline CK gene by restriction mapping and electron microscopy. One MOPC-21 clone corresponds to the gene coding for the MOPC-21 kappa chain polypeptide; it has the V21 gene joined with the CK gene at the J2 sequence. The other MOPC-21 clone corresponds to a nonfunctional rearranged MOPC-21 kappa gene, except for a lkb deletion, 3' of J4. A similar deletion is also found in a "new" kappa gene present in NS-1, a cellular subclone of MOPC-21. The clone of the "nonfunctional" kappa gene has a V gene which is distinct from V21 which is joined to CK in the vicinity of J2. The undeleted form of this gene codes for a KRNA having the size of mature KmRNA which, however, is not translated into kappa chains. Thus the defect of the "nonfunctional" gene manifests itself at a late step of gene expression. The basis for "allelic exclusion" of antibody genes may simply be the complexity of the processes between genes and gene products, resulting in the expression of only one gene.