Biased Igλ expression in hypermutated IgD multiple myelomas does not result from receptor revision

Normal IgM⁻IgD⁺ CD38⁺ B cells and IgM⁻IgD⁺ multiple myelomas (MM) are characterized by Cμ deletion, biased Igλ expression and hypermutated IgV regions. The predominant Igλ usage has been proposed as resulting from secondary Ig gene rearrangements during extensive clonal expansion in the germinal center environment. Here, four cases of IgDλ MM were studied, to address the question of light chain receptor revision in a 'single cell' model. Detailed analyses of both IGK and IGL alleles of each case were performed by Southern blotting, (RT-) PCR, and sequencing. The expressed IgV genes were extensively mutated and Cμ deletion was confirmed in two cases. In addition, in the four MM a total of six non-functional deletional IGK rearrangements were identified, which proved to be unmutated. We conclude that IgD myelomas indeed originate from (post) germinal center B cells in which, in spite of the fact that they are hypermutated, there is no evidence of receptor revision.