Interaction of Human Salivary Gland Epithelial Cells with B Lymphocytes: Implications in the Pathogenesis of Sjögren's Syndrome.

Abstract

Sjögren's syndrome (SS) is characterized by the aberrant activation of B-cells in both the target organs of autoimmune responses, such as the exocrine glands and the periphery. Furthermore, SS is strongly associated with the development of B-cell non-Hodgkin lymphomas, which are considered to result from chronic aberrant activation of B-cells. Disturbances of the minor salivary gland (MSG) infiltrating and peripheral B-cells subpopulations have been described in SS patients; however, the underlying mechanisms have not been uncovered. SG epithelial cells (SGECs) play a key role in the development and organization of MSG lymphocytic infiltrates in SS patients. SGECs are suitably equipped to mediate the recruitment, activation, and differentiation of immune cells in SS, including CD4+-T cells. B-cell activating factor (BAFF) secretion by SGECs suggests that they can also fruitfully interact with B-cells and mediate their activation, differentiation, and disturbed subpopulations in SS. The effect of SGECs in the activation and differentiation of naïve peripheral B-cells, as this attested by phenotypical flow cytometric and cytokine production analyses, is under investigation in the current proposal. This approach is expected to enlighten the mechanisms underlying the aberrant activation and differentiation of B cells in SS and the discovery of novel therapeutic targets for its reversal.