Non-proliferating plasma cells detected in the salivary glands and bone marrow of autoimmune NOD.B10.H2b mice, a model for primary Sjögren’s syndrome

Abstract

Autoantibody secreting plasma cells (PCs) are essential contributors in the development of autoimmune conditions such as primary Sjögren’s syndrome (pSS). Particularly, the long-lived PC subset residing in the bone marrow has shown to continuously produce autoantibodies, whilst remaining unaffected by immunosuppressive treatment. We have previously shown accumulation of potentially long-lived PCs in chronically inflamed salivary glands of pSS patients. In this study, we aimed to characterise the PC compartment in the salivary glands (the target organ for pSS) and bone marrow before the onset of the murine pSS like disease versus advanced diseases progression. Bromodeoxyuridine (BrdU) was incorporated to distinguish the long-lived PCs. Double immunohistochemical staining and immunofluorescence were then conducted on submandibular gland and bone marrow sections from 8- and 40-week-old mice to identify BrdU and CD138. BrdU⁺ cells were detected in the submandibular glands of 8-week-old mice, and observed within all focal infiltrates by 40 weeks of age. Most CD138⁺ PCs were however BrdU⁻ and located predominantly on the periphery of these infiltrates. This observation was verified through immunofluorescence. A comparable staining pattern was observed in the bone marrow of 8- and 40-week-old NOD.B10.H2b mice, where some of the CD138⁺ cells also expressed BrdU. Interestingly, megakaryocytes in the bone marrow of NOD.B10.H2b mice were detected in close proximity to CD138⁺ cells, illustrating a possible presence of PC survival niches. Our results demonstrate the presence and accumulation of potentially long-lived PCs in NOD.B10.H2b mice as the disease advances.

• Autoimmunity
• NOD.B10.H2b mice
• plasma cells
• salivary glands
• Sjögren’s syndrome

Acknowledgements

We gratefully acknowledge Edith Fick, Kjerstin Jakobsen, Gunnvor Øijordsbakken and Marianne Eidsheim for excellent technical assistance.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

This study was supported by the Faculty of Medicine and Dentistry at the University of Bergen, the L. Meltzer Foundation, the Strategic Research Program at Helse Bergen, the Western Regional Health Authority and the Broegelmann Foundation.

Supplementary material available online Supplementary Figure S1