In multiple myeloma clonotypic CD38-/CD19+/CD27+ memory B cells recirculate through bone marrow, peripheral blood and lymph nodes
In multiple myeloma clonotypic CD38-/CD19+/CD27+ memory B cells recirculate through bone marrow, peripheral blood and lymph nodes
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DOI：
10.1080/10428190410001655157
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发表时间：
2004-07-01
影响因子：
2.6
通讯作者：
Johnsen, HE
中科院分区：
文献类型：
--
作者：
Rasmussen, T;Lodahl, M;Johnsen, HE
据信骨髓瘤细胞源自生发中心(GC)或GC后B细胞。 GC B 细胞可以分化为记忆 B 细胞和浆细胞 (PC)。在这项研究中，我们研究了与骨髓瘤 PC 克隆相关的记忆 B 细胞（称为克隆型）的再循环潜力。鉴定了 10 名骨髓瘤患者的骨髓瘤克隆的 V(H)DJ(H) 免疫球蛋白基因重排，并为每位患者设计了等位基因特异性寡核苷酸 (ASO) IgH RT-PCR 检测。将记忆 B 细胞 (CD38(-)/CD19(+)/CD27(+)) 及其由单克隆抗体 CD62L、CCR6、CXCR4、CXCR5、CCR7 定义的亚群作为单细胞进行流式分选，并通过 ASO RT-PCR 分析进行分析。此外，还分析了 7 名完全或部分缓解的骨髓瘤患者的抽吸外周淋巴结 (PLN) 中是否存在克隆型细胞。在 7/10 患者的 PBMNC 中鉴定出循环克隆型记忆 B 细胞，并且鉴定出 CD62L 阳性和阴性克隆型记忆 B 细胞。此外，在 CCR6(+/-) 和 CXCR4(+/-) 记忆 B 细胞亚群中发现克隆型细胞的频率相当，而所有克隆型记忆和后期 B 细胞均为 CXCR5 阳性。根据其免疫表型，在外周血、骨髓和 PLN 中鉴定出了克隆型记忆 B 细胞。大多数骨髓瘤患者体内都存在克隆型记忆 B 细胞，并且似乎具有与正常记忆 B 细胞相同的多样化再循环/归巢能力。
It is believed that myeloma cells are derived from a germinal center ( GC) or post GC B cell. The GC B cell can differentiate into both a memory B cell and a plasma cell (PC). In this study, we investigated the recirculating potential of memory B cells clonally related to the myeloma PC (termed clonotypic). The V(H)DJ(H) immunoglobulin gene rearrangement of the myeloma clone was identified for 10 myeloma patients and allele-specific oligonucleotides (ASO) IgH RT-PCR assays were designed for each patient. Memory B cells (CD38(-)/CD19(+)/CD27(+)) and their subsets defined by the monoclonal antibodies CD62L, CCR6, CXCR4, CXCR5, CCR7 were flow-sorted as single cells and analyzed by ASO RT-PCR analysis. In addition, aspirated peripheral lymph nodes (PLN) of 7 myeloma patients in complete or partial remission were analyzed for the presence of clonotypic cells. Circulating clonotypic memory B cells were identified in PBMNC of 7/10 patients and both CD62L positive and negative clonotypic memory B cells were identified. Furthermore, comparable frequencies of clonotypic cells were found in the CCR6(+/-) and CXCR4(+/-) memory B cell subsets, whereas all clonotypic memory and later stage B cells were CXCR5 positive. In accordance with their immunophenotype, clonotypic memory B-cells were identified in peripheral blood, bone marrow and PLNs. Clonotypic memory B-cells were present in the majority of myeloma patients and seem to have the same diverse recirculating/homing capacity as normal memory B cells.