Bergsagel P L, Smith A M, Szczepek A, Mant M J, Belch A R, Pilarski L M
Department of Immunology, University of Alberta, Edmonton, Canada.
Blood. 1995 Jan 15;85(2):436-47.
Multiple myeloma (MM) is characterized by a plasma cell infiltrate of the bone marrow (BM). However, late-stage monotypic B cells have been detected in the blood. This work analyzes the effects of clinical treatment on late stage CD19+ B cells present in 752 blood samples from 152 MM patients. MM patients have 2 to 8 times as many circulating CD19+ cells as do normal donors. Analysis of the Ig heavy chain (IgH) gene rearrangements using polymerase chain reaction indicates that the CD19+ population includes cells sharing the same clonotypic CDR3 region as is detected in the BM plasma cells, for patients analyzed during chemotherapy or in relapse. They are also monotypic as defined by their cytoplasmic or surface expression of Ig kappa or lambda light chain. The light chain restriction is the same as that of the BM plasma cells. Individual patients observed over 1- to 2-year periods exhibit considerable variation in the number of B cells present in blood; this number does not correlate with the concentration of serum monoclonal Ig. The monoclonal blood CD19+ cells are not eliminated by any of the chemotherapy regimens analyzed and remain at high levels during transient remissions. Patients in the progressive phase of disease or in relapse have significantly higher numbers of B cells than do patients in transient remission or untreated patients. During periods when the quantity of blood B cells approaches normal, phenotypically their quality is highly abnormal, with physical and phenotypic heterogeneity. Most B cells express CD45R0, a high density of CD38, and CD56 characteristic of late-stage B or pre-plasma cells. CD38hi blood B cells had a cyclical presence. We conclude that monoclonal B cells in the blood of myeloma patient populations include drug-resistant reservoirs of clonotypic cells that may underlie relapse.
多发性骨髓瘤（MM）的特征是骨髓（BM）中有浆细胞浸润。然而，在血液中已检测到晚期单克隆B细胞。这项研究分析了临床治疗对152例MM患者752份血样中晚期CD19+B细胞的影响。MM患者循环CD19+细胞的数量是正常供体的2至8倍。使用聚合酶链反应分析免疫球蛋白重链（IgH）基因重排表明，对于化疗期间或复发时分析的患者，CD19+群体包括与BM浆细胞中检测到的具有相同克隆型互补决定区3（CDR3）区域的细胞。根据其细胞质或表面免疫球蛋白κ或λ轻链的表达，它们也是单克隆的。轻链限制与BM浆细胞相同。在1至2年期间观察的个体患者血液中存在的B细胞数量有相当大的差异；这个数量与血清单克隆Ig的浓度无关。所分析的任何化疗方案都不能消除单克隆血液CD19+细胞，并且在短暂缓解期间它们仍保持在高水平。疾病进展期或复发期的患者比短暂缓解期患者或未治疗患者的B细胞数量明显更高。在血液B细胞数量接近正常的时期，其表型质量高度异常，具有物理和表型异质性。大多数B细胞表达CD45R0、高密度的CD38和晚期B细胞或前浆细胞特征性的CD56。CD38高表达的血液B细胞呈周期性出现。我们得出结论，骨髓瘤患者群体血液中的单克隆B细胞包括可能是复发基础的克隆型细胞的耐药库。
