Graft-versus-tumor response in patients with multiple myeloma is associated with antibody response to BCMA, a plasma-cell membrane receptor
Graft-versus-tumor response in patients with multiple myeloma is associated with antibody response to BCMA, a plasma-cell membrane receptor
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DOI：
10.1182/blood-2004-11-4463
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发表时间：
2005-05-15
期刊：
影响因子：
20.3
通讯作者：
Ritz, J
中科院分区：
文献类型：
--
作者：
Bellucci, R;Alyea, EP;Ritz, J
在异基因造血干细胞移植后复发的多发性骨髓瘤患者中，供体淋巴细胞输注（DLIs）可诱导有效的移植物抗肿瘤反应。移植物抗骨髓瘤反应可能主要由供体T细胞介导，但最近的研究也表明，在DLI后完全缓解的患者中，存在针对多种骨髓瘤相关抗原的特异性抗体。在这些研究中发现的B细胞抗原之一是B细胞成熟抗原（BCMA），它是肿瘤坏死因子（TNF）超家族的一种跨膜受体，由成熟B细胞选择性表达。目前的研究是为了在体内描述BCMA抗体的功能意义。通过转染表达BCMA的细胞，发现患者血清中的抗体与BCMA细胞表面结构域发生反应。dli后患者血清能够诱导表达BCMA的转染细胞和原发性骨髓瘤细胞的补体介导裂解和抗体依赖性细胞毒性（ADCC）。BCMA抗体仅在dli后应答者中发现，而在其他同种异体移植患者或健康供体中未发现。这些结果表明BCMA是对DLI有反应的骨髓瘤患者供体b细胞免疫的靶标。体内对细胞表面BCMA的抗体反应可能直接导致肿瘤排斥反应。
Donor lymphocyte infusions (DLIs) induce effective graft-versus-tumor responses in patients with multiple myeloma who relapse after allogeneic hematopoietic stem-cell transplantation. The graft-versus-myeloma response is presumably mediated primarily by donor T cells, but recent studies have also demonstrated the presence of antibodies specific for a variety of myeloma-associated antigens in patients who achieve complete remission after DLI. One of the B-cell antigens identified in these studies was B-cell maturation antigen (BCMA), a transmembrane receptor of the tumor necrosis factor (TNF) superfamily that is selectively expressed by mature B cells. The present studies were undertaken to characterize the functional significance of antibodies to BCMA in vivo. Using transfected cells expressing BCMA, antibodies in patient serum were found to react with the cell-surface domain of BCMA. Post-DLI patient serum was able to induce complement-mediated lysis and antibody-dependent cellular cytotoxicity (ADCC) of transfected cells and primary myeloma cells expressing BCMA. BCMA antibodies were only found in post-DLI responders and not in other allogeneic transplant patients or healthy donors. These results demonstrate that BCMA is a target of donor B-cell immunity in patients with myeloma who respond to DLI. Antibody responses to cell-surface BCMA may contribute directly to tumor rejection in vivo.