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.
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.
a Broegelmann Research Laboratory, Department of Clinical Science , University of Bergen , Bergen , Norway .|b Gade Laboratory for Pathology, Department of Clinical Medicine , University of Bergen , Bergen , Norway , and.
Ewa A
EA
Szyszko
a Broegelmann Research Laboratory, Department of Clinical Science , University of Bergen , Bergen , Norway .
Lara A
LA
Aqrawi
a Broegelmann Research Laboratory, Department of Clinical Science , University of Bergen , Bergen , Norway .
Roland
R
Jonsson
a Broegelmann Research Laboratory, Department of Clinical Science , University of Bergen , Bergen , Norway .
Karl A
KA
Brokstad
b Gade Laboratory for Pathology, Department of Clinical Medicine , University of Bergen , Bergen , Norway , and.|c Department of Pathology , Haukeland University Hospital , Bergen , Norway.
Kathrine
K
Skarstein
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D015551:Autoimmunity; D001853:Bone Marrow / Q000276:immunology* / Q000473:pathology; D001973:Bromodeoxyuridine / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D006801:Humans; D008533:Megakaryocytes / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D010950:Plasma Cells / Q000276:immunology* / Q000473:pathology; D012859:Sjogren's Syndrome / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D013363:Submandibular Gland / Q000276:immunology* / Q000473:pathology; D053668:Syndecan-1 / Q000235:genetics / Q000276:immunology
D001323:Autoantibodies; C508242:Sdc1 protein, mouse; D053668:Syndecan-1; D001973:Bromodeoxyuridine
Autoimmunity; NOD.B10.H2b mice; Sjögren’s syndrome; plasma cells; salivary glands