Perfetti V, Vignarelli M C, Bellotti V, Glennie M J, Zorzoli I, Ubbiali P, Obici L, Massa M, Ippoliti G, Ascari E, Merlini G
Research Laboratories of Biotechnology, University of Pavia-IRCCS Policlinico S. Matteo, Italy.
Lab Invest. 1997 Oct;77(4):333-44.
Circulating clonally related earlier cells are present in multiple myeloma (MM) and may be involved in the dissemination of this disease, its recurrence, and chemoresistance. The nature, stage of differentiation, and size of this cell population remain uncertain. Unlike other B-cell markers, CD22 membrane expression is limited to the late differentiation stages comprised between mature B cells (CD22+) and plasma cells (PC; CD22-) and may thus be useful in delimiting the maturational state of circulating early myeloma cells. Peripheral blood clone-related cells were detected by anti-idiotypic (Id) monoclonal antibodies and found to express CD22 (92% to 95%), monotypic light and heavy chain (100%), and CD38 (45%), whereas bone marrow PC were CD22-negative. CD22 expression was also documented on functional myeloma PC precursors, defined as peripheral blood cells capable of in vitro cytokine-driven monotypic PC differentiation, because up to approximately 70% inhibition of this process was obtained in 10 myeloma patients through the use of biospecific antibodies (BsAb) that deliver the plant toxin saporin to CD22+ cells. As further evidence of CD22 on circulating abnormal cells, it was found that in the only patient analyzed for DNA content, a portion of the peripheral blood CD22+ cells killed were hyperdiploid. Collectively, these findings indicate that most peripheral blood myeloma PC precursors are mature or later B cells presenting membrane CD22. The pattern of CD22 expression suggests the existence in MM of a differentiation process analogous to the normal antigenic response, in which CD22+ B cells migrate to the bone marrow and lose CD22 with PC differentiation. In addition, the sensitivity of myeloma PC precursors to the cytotoxic effects of the anti-CD22 BsAb and the possibility of interfering with their differentiation have potential therapeutic relevance.
循环中克隆相关的早期细胞存在于多发性骨髓瘤（MM）中，可能参与该疾病的传播、复发和化疗耐药。该细胞群体的性质、分化阶段和大小仍不确定。与其他B细胞标志物不同，CD22膜表达仅限于成熟B细胞（CD22+）和浆细胞（PC；CD22-）之间的晚期分化阶段，因此可能有助于界定循环早期骨髓瘤细胞的成熟状态。通过抗独特型（Id）单克隆抗体检测外周血克隆相关细胞，发现其表达CD22（92%至95%）、单型轻链和重链（100%）以及CD38（45%），而骨髓PC为CD22阴性。功能骨髓瘤PC前体细胞也有CD22表达，这些前体细胞定义为能够在体外由细胞因子驱动进行单型PC分化的外周血细胞，因为在10例骨髓瘤患者中，通过使用将植物毒素皂草素递送至CD22+细胞的双特异性抗体（BsAb），该过程受到了约70%的抑制。作为循环异常细胞上CD22的进一步证据，发现在唯一分析了DNA含量的患者中，被杀死的外周血CD22+细胞中有一部分是超二倍体。总体而言，这些发现表明大多数外周血骨髓瘤PC前体细胞是表达膜CD22的成熟或更晚期B细胞。CD22的表达模式表明MM中存在类似于正常抗原反应的分化过程，其中CD22+ B细胞迁移至骨髓并随着PC分化而丢失CD22。此外，骨髓瘤PC前体细胞对抗CD22 BsAb细胞毒性作用的敏感性以及干扰其分化的可能性具有潜在的治疗意义。
