COMPARABLE GENE STRUCTURE OF THE IMMUNOGLOBULIN HEAVY-CHAIN VARIABLE REGION BETWEEN MULTIPLE-MYELOMA AND NORMAL BONE-MARROW LYMPHOCYTES

To characterize multiple myeloma (MM) from the viewpoint of the immuno globulin (Ig) gene structure, we compared the transcripts of the Ig he avy chain variable region from 23 MM samples with 221 clones of the ga mma, alpha and mu chain transcripts amplified by the reverse transcrip tase-polymerase chain reaction (RT-PCR) from normal bone marrow (BM) c ells. The usage of D and J(H) gene segments and the length of the N re gions were the same between MM and the normal gamma, alpha and mu tran scripts. Compared with the known germline V-H genes, the frame work re gions (FWRs) and complementarity determining regions (CDRs) of the V-H segments mutated at rates of 8.3+/-4.7% and 15.9+/-7.7%, respectively , which were the same as the normal gamma and alpha (gamma/alpha) tran scripts and higher than the normal mu transcripts. The replacement/sil ent (RIS) ratios of the mutations in FWRs and CDRs were 1.9+/-1.3 and 2.7+/-1.8, respectively, which were the same as the gamma/alpha and mu transcripts. On the other hand, we detected the clone-specific mu tra nscripts by RT-PCR using the primers corresponding to the each respect ive CDR-III and the constant region of the mu chain in three of the st udied six MM samples, suggesting the involvement of a pre-switched B c ell in some cases of MM. These findings suggested that the cellular or igin of MM is heterogeneous, but that the Ig structure in MM reflects normal B cell maturation to plasma cell through mutation and selection .