Pilarski L M, Masellis-Smith A, Szczepek A, Mant M J, Belch A R
Department of Oncology, University of Alberta, Edmonton, Canada.
Leuk Lymphoma. 1996 Aug;22(5-6):375-83. doi: 10.3109/10428199609054775.
The population of circulating B cells in myeloma patients includes an apparently large but variable subset with the IgH VDJ rearrangement diagnostic for the malignant clone of plasma cells in individual myeloma patients. Although the biological significance is at present unknown, it is likely that they include both malignant and non-malignant clonal relatives of the myeloma plasma cells. This article presents speculations on the significance of these cells in the origin of myeloma and the relationship between monoclonal gammopathy of undetermined significance (MGUS) and frank myeloma. MGUS appears to represent the establishment of clonal dominance probably by a chronically antigen-stimulated B cell clone. It seems likely that malignant transformation event(s) occurring in a clonal daughter cell give rise to myeloma. If correct, this implies that in a myeloma patient, non-malignant antigen-responsive B cells expressing the patient-specific IgH rearrangement coexist in the circulation and probably all lymphoid tissues, with their malignant antigen-independent relatives. However, the significance one attributes to the clonotypic B cells detected in the blood of myeloma patients depends in part on the view one takes of the progression from MGUS to myeloma. An alternative perspective is that MGUS represents a dormant state of malignancy held in check by controlled apoptosis, arrested cell cycling, and/or by immunoregulatory networks. Although lacking in experimental support, if this interpretation were correct, myeloma would occur when the regulatory mechanisms fail, allowing uncontrolled malignant cell renewal. This alternative view would imply that the majority of circulating clonotypic B cells might be malignant. Thus, an analysis of the biology of these clonotypic circulating B cells, with an emphasis on measures of malignancy, is likely to shed considerable light on the events underlying myeloma genesis, progression and spread.
骨髓瘤患者循环B细胞群体中包含一个明显数量众多但存在变数的亚群，其免疫球蛋白重链（IgH）可变区、多样性区和连接区（VDJ）重排可用于诊断个体骨髓瘤患者浆细胞的恶性克隆。尽管其生物学意义目前尚不清楚，但它们可能包括骨髓瘤浆细胞的恶性和非恶性克隆亲属。本文对这些细胞在骨髓瘤起源中的意义以及意义未明的单克隆丙种球蛋白病（MGUS）与显性骨髓瘤之间的关系进行了推测。MGUS似乎代表了可能由长期抗原刺激的B细胞克隆建立的克隆优势。克隆子代细胞中发生的恶性转化事件似乎会导致骨髓瘤。如果这一观点正确，这意味着在骨髓瘤患者中，表达患者特异性IgH重排的非恶性抗原反应性B细胞与它们恶性的抗原非依赖性亲属共存于循环系统以及可能所有的淋巴组织中。然而，人们赋予在骨髓瘤患者血液中检测到的克隆型B细胞的意义部分取决于对从MGUS发展到骨髓瘤过程的看法。另一种观点是，MGUS代表了一种恶性肿瘤的休眠状态，这种状态受到可控的细胞凋亡、细胞周期停滞和/或免疫调节网络的抑制。尽管缺乏实验支持，但如果这种解释正确，当调节机制失效，导致恶性细胞不受控制地更新时，就会发生骨髓瘤。这种另一种观点意味着大多数循环克隆型B细胞可能是恶性的。因此，分析这些克隆型循环B细胞的生物学特性，重点关注恶性程度的衡量指标，可能会为骨髓瘤发生、发展和扩散的潜在机制提供相当多的线索。
