Zehentmeier Sandra, Roth Katrin, Cseresnyes Zoltan, Sercan Özen, Horn Katharina, Niesner Raluca A, Chang Hyun-Dong, Radbruch Andreas, Hauser Anja E
Deutsches Rheuma-Forschungszentrum (DRFZ), Institute of the Leibniz-Gemeinschaft, Berlin, Germany.
Eur J Immunol. 2014 Aug;44(8):2306-17. doi: 10.1002/eji.201344313. Epub 2014 May 30.
In the bone marrow (BM), memory plasma cells (PCs) survive for long time periods in dedicated microenvironmental survival niches, resting in terms of proliferation. Several cell types, such as eosinophils and reticular stromal cells, have been reported to contribute to the survival niche of memory PCs. However, until now it has not been demonstrated whether the niche is formed by a fixed cellular microenvironment. By intravital microscopy, we provide for the first time evidence that the direct contacts formed between PCs and reticular stromal cells are stable in vivo, and thus the PCs are sessile in their niches. The majority (∼ 80%) of PCs directly contact reticular stromal cells in a non-random fashion. The mesenchymal reticular stromal cells in contact with memory PCs are not proliferating. On the other hand, we show here that eosinophils in the vicinity of long-lived PCs are vigorously proliferating cells and represent a dynamic component of the survival niche. In contrast, if eosinophils are depleted by irradiation, newly generated eosinophils localize in the vicinity of radiation-resistant PCs and the stromal cells. These results suggest that memory PC niches may provide attraction for eosinophils to maintain stability with fluctuating yet essential accessory cells.
在骨髓(BM)中,记忆性浆细胞(PCs)在专门的微环境生存龛中长期存活,处于增殖静止状态。据报道,几种细胞类型,如嗜酸性粒细胞和网状基质细胞,有助于记忆性PCs的生存龛形成。然而,到目前为止,尚未证实该龛是否由固定的细胞微环境形成。通过活体显微镜检查,我们首次提供证据表明PCs与网状基质细胞之间形成的直接接触在体内是稳定的,因此PCs在其龛中是固定不动的。大多数(约80%)的PCs以非随机方式直接接触网状基质细胞。与记忆性PCs接触的间充质网状基质细胞不增殖。另一方面,我们在此表明,长寿PCs附近的嗜酸性粒细胞是活跃增殖的细胞,代表了生存龛的动态组成部分。相反,如果通过辐射使嗜酸性粒细胞减少,新产生的嗜酸性粒细胞会定位于抗辐射PCs和基质细胞附近。这些结果表明,记忆性PC龛可能对嗜酸性粒细胞具有吸引力,以与波动但必不可少的辅助细胞维持稳定性。