[Characterization of the immunoglobulin heavy and light chain variable region sequences from human multiple myeloma...

Although multiple myeloma (MM) morphologically represents the terminal B cell differentiated stage as a plasma cell, it remains controversy that MM cells have arisen from a B cell at which stage of B cell development. The immunoglobulin heavy chain (IgH) variable region genes can serve as markers in clonal analysis because unique combinations of VH, D and JH gene elements and as a genealogical record of clonal selection and expansion, and molecular diversification during maturation of the immune response. We analyzed the IgH variable region sequences from human MM cells. Furthermore, to compare with normal bone marrow (BM) plasma cell repertoire, we determined the IgH variable region sequences of PCR amplified cDNA libraries consisting of C mu, C gamma, and C alpha transcripts from human normal BM cells. The VH segments in MM cells, except for Bence-Jones protein (BJP) type, were extensively mutated, and the characteristic structure of the IgH variable region essentially reflect those from normal BM C gamma and C alpha transcripts. Although the replacement/silent (R/S) mutation ration in MM cells was under the value which reflect antigen selected substitutions, such a lower value was also observed in normal BM C gamma and C alpha transcripts, suggesting that the transformation of MM dose not necessarily take place before the antigen-dependent selection, rather can after clonal expansion. However, BJP type MM might arise from an earlier stage of B cell development than the other types because of lower incidence of somatic mutation in their VH segments which was the same as normal BM C mu transcripts.