Juge-Morineau N, Heirman C, Bakkus M, Van Camp B, Malfait R, Harousseau J L, Thielemans K, Bataille R
Department of Hematology, Free University Brussels (VUB), Brussels, Belgium.
Clin Cancer Res. 1997 Dec;3(12 Pt 1):2501-6.
Multiple myeloma (MM) is a B-cell malignancy characterized by the expansion of malignant plasma cells within the bone marrow. Previous studies that have examined the Ig VH genes of IgG and IgA MMs have shown the presence of somatic mutations, suggesting that in these cases, the myeloma precursor cell passed through the phase of antigenic selection within the germinal center but is no longer exposed to the somatic mutation process. However, no information about this matter is available in the rare IgD and IgM MM variants. Therefore, we have analyzed the Ig VH genes of three IgD, one IgM, and one biclonal (IgG and IgM) MM for the presence of somatic mutations. Our study demonstrates that all of these myeloma clones have accumulated a high number of somatic mutations within their Ig VH genes but show no intraclonal variation. Moreover, proof that the clone sustained a strong antigenic selection pressure could be provided in three cases (one IgD and two IgMs). Therefore, this study strongly implies that IgD and IgM MMs emerge from a postgerminal center preswitched B cell that is no longer exposed to the somatic mutation process or able to undergo further isotype switching in vivo.
多发性骨髓瘤（MM）是一种B细胞恶性肿瘤，其特征是骨髓内恶性浆细胞扩增。先前对IgG和IgA MM的Ig VH基因进行检测的研究表明存在体细胞突变，这表明在这些病例中，骨髓瘤前体细胞经历了生发中心内的抗原选择阶段，但不再经历体细胞突变过程。然而，关于罕见的IgD和IgM MM变体，尚无相关信息。因此，我们分析了3例IgD MM、1例IgM MM和1例双克隆（IgG和IgM）MM的Ig VH基因，以检测体细胞突变的存在情况。我们的研究表明，所有这些骨髓瘤克隆在其Ig VH基因内都积累了大量体细胞突变，但未显示出克隆内变异。此外，在3例病例（1例IgD MM和2例IgM MM）中，可以证明克隆承受了强烈的抗原选择压力。因此，本研究强烈提示，IgD和IgM MM起源于生发中心后已发生类别转换的B细胞，该细胞不再经历体细胞突变过程，也无法在体内进一步发生类别转换。
