Jensen G S, Belch A R, Kherani F, Mant M J, Ruether B A, Pilarski L M
Department of Immunology, University of Alberta, Edmonton, Canada.
Scand J Immunol. 1992 Dec;36(6):843-53. doi: 10.1111/j.1365-3083.1992.tb03146.x.
Circulating monoclonal B cells in peripheral blood from patients with multiple myeloma or with monoclonal gammopathy of undetermined significance (MGUS) have previously been shown to express CD19, CD20, and PCA-1 and are predominantly CD45R0+, characterizing them as very late stage B cells. This work shows that the abnormal B cells are monoclonal as defined by their exclusive expression of either kappa or lambda light chain mRNA, and that the same type of light chain mRNA is expressed in both bone marrow plasma cells and blood B cells. These abnormal tumour-related circulating B cells express high densities of CD11b, a beta 2-integrin, which is expressed in a conformationally active state as defined by reactivity with monoclonal antibody 7E3. Normal peripheral blood B cells which do not bear CD11b acquire a high density after stimulation with pokeweed mitogen (PWM). At day 4 of culture, the expression of CD11b on normal CD19+ B cells was nearly comparable to that of the circulating myeloma late stage B cells. After PWM stimulation of circulating myeloma B cells the expression of CD11b was gradually lost during 4 days of culture, suggesting that its expression is dynamically regulated. Two patients with no phenotypically abnormal B cells in their blood at diagnosis acquired a large subset of CD11b+ B cells 4 weeks after initiation of chemotherapy. In most patients, a subset of the circulating myeloma B cells express a low density of CD5. The proportion of CD19+ B cells in the bone marrow expressing CD11b was much reduced compared with peripheral blood B cells, and CD11b was not detectable on plasma cells in the bone marrow, suggesting a sequential relationship of the B-cell subsets detected in our population of patients, involving gradual loss of CD11b concurrent with the loss of CD19 during B lineage differentiation. These cells appear to represent a continuously differentiating monoclonal B lineage culminating in the CD11b- plasma cell entrenched in the bone marrow. We speculate that the expression of conformationally active CD11b on the abnormal B cells in peripheral blood mononuclear cells of myeloma patients facilitates transendothelial migration of circulating myeloma B cells to the bone marrow.
先前已表明，多发性骨髓瘤患者或意义未明的单克隆丙种球蛋白病（MGUS）患者外周血中的循环单克隆B细胞表达CD19、CD20和PCA-1，且主要为CD45R0+，这表明它们是非常晚期的B细胞。这项研究表明，异常B细胞是单克隆的，这是由其κ或λ轻链mRNA的排他性表达所定义的，并且相同类型的轻链mRNA在骨髓浆细胞和血液B细胞中均有表达。这些与肿瘤相关的异常循环B细胞表达高密度的CD11b，一种β2整合素，其以与单克隆抗体7E3反应所定义的构象活性状态表达。不表达CD11b的正常外周血B细胞在用商陆有丝分裂原（PWM）刺激后会获得高密度的CD11b。在培养的第4天，正常CD19+B细胞上CD11b的表达与循环骨髓瘤晚期B细胞的表达几乎相当。在用PWM刺激循环骨髓瘤B细胞后，CD11b的表达在4天的培养过程中逐渐丧失，这表明其表达是动态调节的。两名诊断时血液中无表型异常B细胞的患者在化疗开始4周后获得了大量CD11b+B细胞亚群。在大多数患者中，循环骨髓瘤B细胞亚群表达低密度的CD5。与外周血B细胞相比，骨髓中表达CD11b的CD19+B细胞比例大幅降低，并且在骨髓浆细胞上未检测到CD11b，这表明在我们的患者群体中检测到的B细胞亚群存在顺序关系，涉及在B细胞谱系分化过程中CD11b与CD19的逐渐丧失。这些细胞似乎代表了一个持续分化的单克隆B谱系，最终形成骨髓中固定的CD11b-浆细胞。我们推测，骨髓瘤患者外周血单个核细胞中异常B细胞上构象活性CD11b的表达促进了循环骨髓瘤B细胞向骨髓的跨内皮迁移。
