Division of Cancer Medicine, Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
J Immunol. 2013 May 1;190(9):4887-98. doi: 10.4049/jimmunol.1300179. Epub 2013 Mar 27.
Ag activation of the BCR may play a role in the pathogenesis of human follicular lymphoma (FL) and other B cell malignancies. However, the nature of the Ag(s) recognized by tumor BCRs has not been well studied. In this study, we used unbiased approaches to demonstrate that 42 (19.35%) of 217 tested FL Igs recognized vimentin as a shared autoantigen. The epitope was localized to the N-terminal region of vimentin for all vimentin-reactive tumor Igs. We confirmed specific binding to vimentin by using recombinant vimentin and by performing competitive inhibition studies. Furthermore, using indirect immunofluorescence staining, we showed that the vimentin-reactive tumor Igs colocalized with an anti-vimentin mAb in HEp-2 cells. The reactivity to N-terminal vimentin of IgG FL Igs was significantly higher than that of IgM FL Igs (30.4 versus 10%; p = 0.0022). However, vimentin-reactive FL Igs did not share CDR3 motifs and were not homologous. Vimentin was expressed in the T cell-rich regions of FL, suggesting that vimentin is available for binding with tumor BCRs within the tumor microenvironment. Vimentin was also frequently recognized by mantle cell lymphoma and multiple myeloma Igs. Our results demonstrate that vimentin is a shared autoantigen recognized by nonstereotyped FL BCRs and by the Igs of mantle cell lymphoma and multiple myeloma and suggest that vimentin may play a role in the pathogenesis of multiple B cell malignancies. These findings may lead to a better understanding of the biology and natural history of FL and other B cell malignancies.
BCR 的 Ag 激活可能在人类滤泡性淋巴瘤 (FL) 和其他 B 细胞恶性肿瘤的发病机制中发挥作用。然而，肿瘤 BCR 识别的 Ag(s) 的性质尚未得到很好的研究。在这项研究中，我们使用无偏方法证明，在测试的 217 个 FL Ig 中，有 42 个（19.35%）识别波形蛋白作为共同自身抗原。对于所有波形蛋白反应性肿瘤 Ig，表位定位于波形蛋白的 N 端区域。我们通过使用重组波形蛋白和进行竞争抑制研究证实了与波形蛋白的特异性结合。此外，通过间接免疫荧光染色，我们显示波形蛋白反应性肿瘤 Ig 与抗波形蛋白 mAb 在 HEp-2 细胞中共定位。IgG FL Ig 对 N 端波形蛋白的反应性明显高于 IgM FL Ig（30.4 对 10%；p = 0.0022）。然而，波形蛋白反应性 FL Ig 没有共享 CDR3 基序，也不是同源的。波形蛋白在 FL 的 T 细胞丰富区表达，这表明在肿瘤微环境中，波形蛋白可与肿瘤 BCR 结合。波形蛋白也经常被套细胞淋巴瘤和多发性骨髓瘤 Ig 识别。我们的结果表明，波形蛋白是未定型 FL BCR 以及套细胞淋巴瘤和多发性骨髓瘤 Ig 识别的共同自身抗原，并表明波形蛋白可能在多种 B 细胞恶性肿瘤的发病机制中发挥作用。这些发现可能导致更好地理解 FL 和其他 B 细胞恶性肿瘤的生物学和自然史。
