Comparable gene structure of the immunoglobulin heavy chain variable region between multiple myeloma and normal bone marrow lymphocytes

Abstract

To characterize multiple myeloma (MM) from the viewpoint of the immunoglobulin (Ig) gene structure, we compared the transcripts of the Ig heavy chain variable region from 23 MM samples with 221 clones of the gamma, alpha and mu chain transcripts amplified by the reverse transcriptase-polymerase chain reaction (RT-PCR) from normal bone marrow (BM) cells. The usage of D and JH gene segments and the length of the N regions were the same between MM and the normal gamma, alpha and mu transcripts. Compared with the known germline VH genes, the frame work regions (FWRs) and complementarity determining regions (CDRs) of the VH 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) transcripts and higher than the normal mu transcripts. The replacement/silent (R/S) 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 transcripts by RT-PCR using the primers corresponding to the each respective CDR-III and the constant region of the mu chain in three of the studied six MM samples, suggesting the involvement of a pre-switched B cell in some cases of MM. These findings suggested that the cellular origin of MM is heterogeneous, but that the Ig structure in MM reflects normal B cell maturation to plasma cell through mutation and selection.