Static and dynamic components synergize to form a stable survival niche for bone marrow plasma cells.
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.
Deutsches Rheuma-Forschungszentrum (DRFZ), Institute of the Leibniz-Gemeinschaft, Berlin, Germany.
Sandra
S
Zehentmeier
Katrin
K
Roth
Zoltan
Z
Cseresnyes
Özen
Ö
Sercan
Katharina
K
Horn
Raluca A
RA
Niesner
Hyun-Dong
HD
Chang
Andreas
A
Radbruch
Anja E
AE
Hauser
D000818:Animals; D001853:Bone Marrow / Q000276:immunology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D048708:Cell Growth Processes / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D060833:Cellular Microenvironment / Q000276:immunology; D004804:Eosinophils / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology; D051379:Mice; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology*
Bone marrow; Intravital microscopy; Plasma cells; Stromal cells; Survival niche