Diaw L, Siwarski D, DuBois W, Jones G, Huppi K
Laboratory of Genetics, National Cancer Institute/NIH, Building 37, Rm. 2B-21, Bethesda, MD 20892, USA.
Mol Immunol. 2000 Aug-Sep;37(12-13):775-81. doi: 10.1016/s0161-5890(00)00100-0.
Rearrangement of the light chain locus is believed to be an ordered process in which Iglambda rearrangements only occur if Igkappa rearrangements are found to be non-productive or self-reactive. Secondary rearrangements of the B-cell receptor (BCR) have shown, however, that rescue of abortive Igkappa rearrangements or autoreactive B cells can be achieved through receptor editing using upstream V-regions as the template sequences. Since secondary rearrangement can occur in the periphery, possibly in a subset of B cells maintaining constitutive Rag activity, it is conceivable that two light chains (kappa:kappa or kappa:lambda) could be expressed in these cells, apparently in violation of allelic exclusion. Previously, we have reported that silicone-induced plasmacytomas (SIPCs) exhibit dual expression and ongoing rearrangements of Igkappa and Iglambda. In this paper, we show by ELISA that both Igkappa and Iglambda are found at the protein level, but are secreted in different amounts. Furthermore, we demonstrate by micro-manipulation and RT-PCR amplification that Igkappa and Iglambda are simultaneously expressed in a single SIPC cell. We propose that these dual-expressing cells, found intermittently in cases of plasmacytomas (PCs), may have originally been immature B cells when transformed but now are maintained as a long-lived mature B cell found infrequently in the tumor population.
轻链基因座的重排被认为是一个有序的过程,在这个过程中,只有当发现Igκ重排是非 productive 或自身反应性时,Igλ重排才会发生。然而,B细胞受体(BCR)的二次重排表明,通过使用上游V区作为模板序列进行受体编辑,可以挽救流产的Igκ重排或自身反应性B细胞。由于二次重排可能发生在外周,可能在维持组成型Rag活性的B细胞亚群中,因此可以想象,这些细胞中可能会表达两条轻链(κ:κ或κ:λ),这显然违反了等位基因排斥。此前,我们报道过硅诱导的浆细胞瘤(SIPC)表现出Igκ和Igλ的双重表达以及持续重排。在本文中,我们通过ELISA表明,在蛋白质水平上同时发现了Igκ和Igλ,但它们的分泌量不同。此外,我们通过显微操作和RT-PCR扩增证明,Igκ和Igλ在单个SIPC细胞中同时表达。我们提出,这些在浆细胞瘤(PC)病例中间歇性发现的双重表达细胞,在转化时可能原本是未成熟B细胞,但现在作为肿瘤群体中罕见的长寿成熟B细胞维持下来。