Abstract
The risk of developing lymphoma in patients with Sjögren’s syndrome (SS) is 44 times higher than in the normal population with the most common lymphomas derived from marginal zone B (MZB) cells. Current understanding of the role of MZB cells in SS is primarily based on salivary gland pathology, while their contextual association with lacrimal glands and ocular manifestations largely remains unknown. We examined this possibility using a SS mouse model (thrombospondin-1 deficient (TSP1−/−)) with well-characterized ocular disease. We determined the frequency, localization, and cytokine profiles of MZB cells and their association with an antibody response in TSP1−/− mice treated with a TSP-derived peptide. A significantly increased frequency of MZB cells was detected in the spleens and lacrimal glands of TSP1−/− mice in comparison to wild-type tissues as detected by immunostaining. An altered cytokine profile of TSP1−/− MZB cells was supportive of T helper 17 (Th17)-related pathogenesis. A significantly reduced antibody response and the splenic MZB compartment against an eye-derived antigen were noted in TSP-derived peptide-treated mice. These changes correspond with the previously reported ability of the peptide to ameliorate SS-related ocular manifestations. Collectively, our results demonstrate dysregulation of MZB cells in TSP1−/− mice and highlight their role in the context of SS-related chronic ocular surface disease.
Highlights
Sjögren’s syndrome (SS) is a rheumatic disease that affects both the oral and ocular mucosa, as salivary and lacrimal glands are targeted by the autoimmune response
To determine if the B-cell phenotype in their spleens correlates with the autoimmune pathology, we examined surface IgM and IgG expression on B cells (B220+) in the spleens harvested from 13-week-old wild-type (WT) or TSP1−/− mice
Increased numbers of IgM+ memory B cells detected in the periphery and salivary glands of SS patients were identified as Marginal zone B (MZB) cells [4,25], which are implicated in local antibody production and subsequent destruction of glandular epithelial cells
Summary
Sjögren’s syndrome (SS) is a rheumatic disease that affects both the oral and ocular mucosa, as salivary and lacrimal glands are targeted by the autoimmune response. The main histopathological feature of SS is periductal aggregates of mononuclear cells in the glands comprised of T and B lymphocytes. Larger aggregates forming germinal center-like structures are reported in salivary glands and are derived from hyperreactive B cells associated with autoantibodies commonly detected in SS patients [1]. Non-Hodgkin’s B-cell lymphoma is a most serious complication of SS with the most common being low-grade marginal zone lymphomas [3]. Marginal zone B (MZB) cells were reported in the lymphocyte infiltrates of salivary glands in SS patients and are implicated in local production of autoantibodies and subsequent glandular destruction [4]. The presence of MZB cells in lacrimal glands during SS remains to be elucidated
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