摘要

PURPOSE:Reduced uninvolved immunoglobulin (Ig) levels are a hallmark of multiple myeloma. We previously showed that B-cell maturation antigen (BCMA) is solubilized and at high levels in multiple myeloma patient serum. We hypothesize that soluble BCMA binds B-cell-activating factor (BAFF) preventing its function to stimulate late B cells, and would result in lower polyclonal antibody levels in these patients.
EXPERIMENTAL DESIGN:Mice were dosed with recombinant human BCMA (rhBCMA) and BCMA-BAFF complexes were analyzed in plasma, and its effects on antibody and Ig heavy chain mRNA levels determined. Using flow cytometry, BAFF binding to B cells was examined in the presence of rhBCMA and sera from multiple myeloma patients. In multiple myeloma sera, BCMA-BAFF complex formation and BCMA, IgA, IgG levels, and heavy-light chain isoform pair levels were determined.
RESULTS:rhBCMA-BAFF complexes formed in immune-competent and deficient mice. Mice with human multiple myeloma xenografts, which contain plasma hBCMA and hBCMA-BAFF complexes, showed reduced plasma-free BAFF levels. rhBCMA administered to immune competent mice markedly reduced plasma IgA, IgG, and IgM levels and splenic Ig heavy chain mRNA levels. In serum from multiple myeloma patients, BCMA-BAFF complexes were detected and BAFF levels were reduced. Multiple myeloma patient sera containing BCMA prevented binding of BAFF to B cells. There is an inverse correlation between serum BCMA and uninvolved polyclonal Ig level in multiple myeloma patients.
CONCLUSIONS:Our results show that soluble BCMA sequesters circulating BAFF, thereby preventing it from performing its signaling to stimulate normal B-cell and plasma cell development, resulting in reduced polyclonal antibody levels in multiple myeloma patients. Clin Cancer Res; 22(13); 3383-97. ©2016 AACR.

译文

目的: 未参与的免疫球蛋白 (Ig) 水平降低是多发性骨髓瘤的标志。我们先前表明 b细胞成熟抗原 (BCMA) 是可溶的,并且在多发性骨髓瘤患者血清中处于高水平。我们假设可溶性 BCMA 结合 b细胞激活因子 (BAFF) 阻止其刺激晚期 b细胞的功能,并将导致这些患者的多克隆抗体水平降低。
实验设计: 给小鼠注射重组人 BCMA (rhBCMA),分析血浆中 BCMA-BAFF 复合物,并测定其对抗体和 Ig 重链 mRNA 水平的影响。使用流式细胞术,在存在 rhBCMA 的情况下检查 BAFF 与 b细胞的结合以及来自多发性骨髓瘤患者的血清。在多发性骨髓瘤血清中,BCMA-BAFF 复合物的形成和 BCMA 、 IgA 、 IgG 水平以及重轻链亚型对水平被测定。
结果: 免疫活性和缺陷小鼠中形成 rhBCMA-BAFF 复合物。含有血浆 hBCMA 和 hBCMA-BAFF 复合物的人多发性骨髓瘤异种移植小鼠显示血浆游离 BAFF 水平降低。给予免疫活性小鼠 rhBCMA 显著降低血浆 IgA 、 IgG 和 IgM 水平和脾脏 Ig 重链 mRNA 水平。在多发性骨髓瘤患者的血清中,检测到 BCMA-BAFF 复合物,BAFF 水平降低。含 BCMA 的多发性骨髓瘤患者血清阻止 BAFF 与 b细胞结合。血清 BCMA 和未参与的多克隆 Ig 水平在多发性骨髓瘤患者中存在负相关。
结论: 我们的结果表明,可溶性 BCMA 隔离循环 BAFF,从而阻止其执行刺激正常 b细胞和浆细胞发育的信号传导, 导致多发性骨髓瘤患者的多克隆抗体水平降低。Clin Cancer Res; 22 (13); 3383-97。©2016 AACR。

B Cell Maturation Antigen

肿瘤 靶向治疗 临床研究术语
概述  :  

B细胞表面成熟抗原(BCMA),也叫做肿瘤坏死因子受体超家族成员17(TNFRSF17, tumor necrosis factor receptor superfamily, member 17)或者CD269。是一种浆细胞选择性的蛋白,最早发现于成熟B淋巴细胞表面,在其他组织细胞中几乎不表达。BCMA在恶性增殖的B淋巴细胞(例如骨髓瘤细胞、白血病细胞)中高度表达,同时其介导下游信号通路,对肿瘤细胞的存活、增殖、转移和耐药起着关键性的作用。正因为BCMA的这些特征,使其成为了免疫

Maturation   英 /mætjʊ'reɪʃ(ə)n/   美 /,mætʃu'reʃən/ 

       n. 成熟;化脓;生殖细胞之形成

       Another candle adds another maturation to the charm of your life.  蜡烛每增添一支,你的生命又增添了多一分的成熟风韵。

               

Antigen   英 /'æntɪdʒ(ə)n/   美 /'æntɪdʒən/

       n. [免疫] 抗原

       The attraction between an antigen and an antibody.  抗原和抗体之间的相互吸引力。

请扫描右侧二维码,免费查看词汇专业知识背景