Dysregulated Marginal Zone B Cell Compartment in a Mouse Model of Sjögren’s Syndrome with Ocular Inflammation

摘要

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.