Mass cytometry analysis shows that a novel memory phenotype B cell is expanded in multiple myeloma.
Mass cytometry analysis shows that a novel memory phenotype B cell is expanded in multiple myeloma.
复制标题
DOI：
10.1158/2326-6066.cir-14-0236-t
复制
发表时间：
2015-06
影响因子：
10.1
通讯作者：
Davis MM
中科院分区：
文献类型：
--
作者：
Hansmann L;Blum L;Ju CH;Liedtke M;Robinson WH;Davis MM
如果能够从血液样本中确定癌症的状态，这将是非常有益的。然而，外周血白细胞在个体之间是非常异质的，因此可能需要高分辨率技术。我们使用飞行时间流式细胞术（CyTOF）和下一代测序来询问浆细胞癌（多发性骨髓瘤）和相关癌前状态是否对患者的外周血单核细胞表型有任何一致的影响。对来自13名癌症患者、9名癌前患者和9名健康个体的外周血样本的分析揭示了T、B和自然杀伤细胞区室的频率的显著差异。最引人注目的是，我们发现了一种新的B细胞群，通常占总B细胞的4.0±0.7%（平均值±SD），在多发性骨髓瘤活动性疾病患者中扩增高达13倍。该人群表达先前与记忆（CD27+）和幼稚（CD24loCD38+）表型相关的标志物。单细胞免疫球蛋白基因测序显示多克隆性，表明这些细胞不是骨髓瘤的前体细胞，也不是记忆细胞的特征体细胞突变。SYK、ERK和p38磷酸化反应，以及这些细胞中大多数表达IgM或IgD以外的同种型的事实，证实了该群体的记忆特征，将其定义为一种新型的记忆B细胞。
It would be very beneficial if the status of cancers could be determined from a blood specimen. However, peripheral blood leukocytes are very heterogeneous between individuals and thus high resolution technologies are likely required. We used cytometry by time-of-flight (CyTOF) and next generation sequencing to ask whether a plasma cell cancer (multiple myeloma) and related pre-cancerous states had any consistent effect on the peripheral blood mononuclear cell phenotypes of patients. Analysis of peripheral blood samples from 13 cancer patients, 9 pre-cancer patients, and 9 healthy individuals revealed significant differences in the frequencies of the T, B, and natural killer cell compartments. Most strikingly, we identified a novel B-cell population that normally accounts for 4.0±0.7% (mean±SD) of total B cells and is up to 13-fold expanded in multiple myeloma patients with active disease. This population expressed markers previously associated with both memory (CD27+) and naïve (CD24loCD38+) phenotypes. Single-cell immunoglobulin gene sequencing showed polyclonality, indicating that these cells are not precursors to the myeloma, and somatic mutations, a characteristic of memory cells. SYK, ERK, and p38 phosphorylation responses, and the fact that most of these cells expressed isotypes other than IgM or IgD, confirmed the memory character of this population, defining it as a novel type of memory B cells.