Nuclear BCL10 in primary Sjögren's syndrome.

BACKGROUND: The events following triggering of antigen receptors and subsequent activation of the transcription factor nuclear factor kappa B (NFkappaB) need to be carefully controlled to prevent abnormal immune responses. BCL10 links the antigen receptor to NFkappaB. The aim of this study was to determine the expression pattern of BCL10 and NFkappaB in minor salivary gland infiltrates of patients with primary Sjögren's syndrome (pSS). METHODS: Minor salivary glands from patients with primary SS (n = 17) and sicca controls (n = 4) were evaluated by single and double immunohistochemistry and immunofluorescence for confocal microscopy. BCL10 and NFkappaB-p65 expression were evaluated in the infiltrating lymphocytes. Ectopic germinal centers (GCs) were investigated by CD21. Tonsil, lymph node and lymphoma tissue were used as positive controls. RESULTS: BCL10 nuclear positive cells were observed in focal lymphocytic infiltrates in the investigated minor salivary glands and were not restricted to patients with ectopic GCs. By double-staining, some of the BCL10 nuclear positive cells were identified as B cells. There was, however, no constitutive activation of NFkappaB as depicted by the exclusive cytoplasmic expression of p65 in the infiltrating lymphocytes in the pSS. CONCLUSION: Nuclear expression of BCL10 in infiltrating lymphocytes was a common occurrence in pSS minor salivary glands indicating it as a possible marker of autoimmune induced chronic inflammation. There was, however, no constitutive activation of NFkappaB.

Evaluation of usage of virtual microscopy for the study of histology in the medical, dental, and veterinary undergraduate programs of a UK University.

This article describes the introduction of a virtual microscope (VM) that has allowed preclinical histology teaching to be fashioned to better suit the needs of approximately 900 undergraduate students per year studying medicine, dentistry, or veterinary science at the University of Bristol, United Kingdom. Features of the VM implementation include: (1) the facility for students and teachers to make annotations on the digital slides; (2) in-house development of VM-based quizzes that are used for both formative and summative assessments; (3) archiving of teaching materials generated each year, enabling students to access their personalized learning resources throughout their programs; and (4) retention of light microscopy capability alongside the VM. Student feedback on the VM is particularly positive about its ease of use, the value of the annotation tool, the quizzes, and the accessibility of all components off-campus. Analysis of login data indicates considerable, although variable, use of the VM by students outside timetabled teaching. The median number of annual logins per student account for every course exceeded the number of timetabled histology classes for that course (1.6­3.5 times). The total number of annual student logins across all cohorts increased from approximately 9,000 in the year 2007­2008 to 22,000 in the year 2010­2011. The implementation of the VM has improved teaching and learning in practical classes within the histology laboratory and facilitated consolidation and revision of material outside the laboratory. Discussion is provided of some novel strategies that capitalize on the benefits of introducing a VM, as well as strategies adopted to overcome some potential challenges.

Blockade of lymphotoxin-beta receptor signaling reduces aspects of Sjögren's syndrome in salivary glands of non-obese diabetic mice.

INTRODUCTION: The lymphotoxin-beta receptor (LTbetaR) pathway is important in the development and maintenance of lymphoid structures. Blocking this pathway has proven beneficial in murine models of autoimmune diseases such as diabetes and rheumatoid arthritis. The aim of this study was to determine the effects of LTbetaR pathway blockade on Sjögren syndrome (SS)-like salivary gland disease in non-obese diabetic (NOD) mice. METHODS: The course of SS-like disease was followed in NOD mice that were given lymphotoxin-beta receptor-immunoglobulin fusion protein (LTbetaR-Ig) starting at 9 weeks of age. Treatment was given as a single weekly dose for 3, 7, or 10 weeks. Age-matched NOD mice treated with mouse monoclonal IgG1, or not treated at all, were used as controls. The severity of inflammation, cellular composition, and lymphoid neogenesis in the submandibular glands were determined by immunohistochemistry. Mandibular lymph nodes were also studied. Saliva flow rates were measured, and saliva was analyzed by a multiplex cytokine assay. The salivary glands were analyzed for CXCL13, CCL19, and CCL21 gene expression by quantitative polymerase chain reaction. RESULTS: Treatment with LTbetaR-Ig prevented the increase in size and number of focal infiltrates normally observed in this SS-like disease. Compared with the controls, the submandibular glands of LTbetaR-Ig-treated mice had fewer and smaller T- and B-cell zones and fewer high endothelial venules per given salivary gland area. Follicular dendritic cell networks were lost in LTbetaR-Ig-treated mice. CCL19 expression was also dramatically inhibited in the salivary gland infiltrates. Draining lymph nodes showed more gradual changes after LTbetaR-Ig treatment. Saliva flow was partially restored in mice treated with 10 LTbetaR-Ig weekly injections, and the saliva cytokine profile of these mice resembled that of mice in the pre-disease state. CONCLUSIONS: Our findings show that blocking the LTbetaR pathway results in ablation of the lymphoid organization in the NOD salivary glands and thus an improvement in salivary gland function.