CD19
骨髓
CD38
表型
免疫学
生物
抗体
抗原
分子生物学
等离子体电池
B细胞
川地34
细胞生物学
干细胞
遗传学
基因
作者
Syed Saad Mujtahedi,Furkan Yigitbilek,Xiomara Benavides,Massini Merzkani,Elif Ozdogan,Omar Abozied,Natalie A. Moore,Walter D. Park,Mark D. Stegall
标识
DOI:10.1016/j.trim.2022.101726
摘要
Bone marrow-derived long-lived plasma cells (LLPCs) are thought to be a major source of alloantibody in sensitized transplant patients. However, studies of LLPCs have been hampered not only by the fact that they are rare and difficult to isolate and culture but also due to the lack of consensus regarding a definitive cell-surface phenotype. The goal of the current study was to determine if LLPCs have a specific, stable cell-surface phenotype. PCs were isolated from high-volume (120cc) bone marrow aspirates that were enriched first by negative selection then positive selection using anti-CD38 antibody-coated beads and purified by cell sorting. A typical isolation resulted in >100,000 PCs that were sorted into 4 populations with variable numbers of PCs: CD19+/CD138+/CD38Hi (64.1% of the PCs), CD19-/CD138+/CD38Hi (20.9%), CD19+/CD138-/CD38Hi (10.7%), and CD19-/CD138-/CD38Hi (4.3%). The purity of each subset was 96-99%. Each subset contained PCs secreting IgG and IgA. Measles- and tetanus-specific PCs (i.e. putative IgG secreting, antigen-specific LLPCs). LLPCs were identified in both the CD19+/CD138+/CD38Hi and CD19-/CD138+/CD38Hi subsets and in the smaller CD138- subsets (when pooled). Thus, all CD38Hi subsets contained LLPCs. Cultured PCs maintained viability (>50%) and function and could be retrieved for analyses. During 7 days of culture, cell surface expression changed from baseline in many PCs. For example, approximately 20% of CD19 + CD138+/CD38Hi cells (the largest PC subset) became CD19-. CFSE assays showed no division and only a small percentage of LLPCs were Ki-67 positive suggesting that the cells did not divide in culture and that the antibody detected was not from plasmablasts. We conclude that human bone marrow LLPCs have a heterogeneous expression of CD19 and CD138, which can change during cell culture. The fact that LLPCs were found in all four subsets raises the possibility that a large percentage of PCs in the bone marrow may be LLPCs.
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