Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University, Seiryo-machi, Sendai, Japan.
Division of Molecular and Regenerative Prosthodontics, Tohoku University Graduate School of Dentistry, Seiryo-machi, Sendai, Japan.
Int Immunol. 2018 May 24;30(6):241-253. doi: 10.1093/intimm/dxy018.
Plasma cells (PCs) acquiring long lifespans in the bone marrow (BM) play a pivotal role in the humoral arm of immunological memory. The PCs reside in a special BM niche and produce antibodies against past-encountered pathogens or vaccine components for a long time. In BM, cysteine-X-cysteine (CXC) chemokine receptor type 4 (CXCR4)-expressing PCs and myeloid cells such as dendritic cells are attracted to and held by CXC chemokine ligand 12 (CXCR12)-secreting stromal cells, where survival of the PCs is supported by soluble factors such as IL-6 and APRIL (a proliferation-inducing ligand) produced by neighboring myeloid cells. Although these stromal cells are also supposed to be involved in the support of the survival and antibody production, the full molecular mechanism has not been clarified yet. Here, we show that BM PDGFRα+Sca-1+-enriched mesenchymal stem cells (MSCs), which can contribute as stromal cells for hematopoietic stem cells, also support in vitro survival of and antibody production by BM PCs. IL-6 produced by MSCs was found to be involved in the support. Immunohistochemistry of BM sections suggested a co-localization of a minor population of PCs with PDGFRα+Sca-1+ MSCs in the BM. We also found that the sort-purified MSC preparation was composed of multiple cell groups with different gene expression profiles, as found on single-cell RNA sequencing, to which multiple roles in the in vitro PC support could be attributed.
浆细胞（PCs）在骨髓（BM）中获得长寿命，在免疫记忆的体液 arm 中发挥关键作用。PCs 存在于特殊的 BM 龛位中，并长时间产生针对过去遇到的病原体或疫苗成分的抗体。在 BM 中，表达半胱氨酸-X-半胱氨酸（CXC）趋化因子受体 4（CXCR4）的 PCs 和树突状细胞等髓系细胞被吸引并被 CXC 趋化因子配体 12（CXCR12）分泌的基质细胞所保留，其中 PCs 的存活由相邻髓系细胞产生的可溶性因子（如 IL-6 和 APRIL（增殖诱导配体））支持。尽管这些基质细胞也应该参与支持 PC 的存活和抗体产生，但完整的分子机制尚未阐明。在这里，我们表明 BM PDGFRα+Sca-1+丰富的间充质干细胞（MSCs），可以作为造血干细胞的基质细胞，也支持 BM PCs 的体外存活和抗体产生。发现由 MSCs 产生的 IL-6 参与了支持。BM 切片的免疫组织化学显示，少数 PC 与 PDGFRα+Sca-1+ MSCs 在 BM 中存在共定位。我们还发现，经分选纯化的 MSC 制剂由多个具有不同基因表达谱的细胞群组成，如单细胞 RNA 测序所示，这些细胞群可能在体外 PC 支持中发挥多种作用。
