IMMUNOGLOBULIN-D AND IMMUNOGLOBULIN-M MULTIPLE-MYELOMA VARIANTS ARE HEAVILY MUTATED

Multiple myeloma (MM) is a B-cell malignancy characterized by the expa nsion of malignant plasma cells within the bone marrow, Previous studi es that have examined the Ig V-H genes of IgG and IgA MR3s have shown the presence of somatic mutations, suggesting that in these cases, the myeloma precursor cell passed through the phase of antigenic selectio n within the germinal center but is no longer exposed to the somatic m utation process, However, no information about this matter is availabl e in the rare IgD and IgM MM variants. Therefore, we have analyzed the Ig V-H genes of three IgD, one IgM, and one biclonal (IgG and IgM) MM for the presence of somatic mutations, Our study demonstrates that al l of these myeloma clones have accumulated a high number of somatic mu tations within their Ig V-H genes but show no intraclonal variation, M oreover, proof that the clone sustained a strong antigenic selection p ressure could be provided in three cases (one IgD and two IgMs). There fore, this study strongly implies that IgD and IgM MMs emerge from a p ostgerminal center preswitched B cell that is no longer exposed to the somatic mutation process or able to undergo further isotype switching in vivo.