A dual role of osteopontin in modifying B cell responses

Abstract

Abstract Background The occurrence of B cell aggregates within the central nervous system (CNS) has prompted investigation of the potential sources of pathogenic B cell and T cell responses in a subgroup of secondary progressive multiple sclerosis (MS) patients. Nevertheless, the expression profile of molecules associated with these aggregates and their role in aggregate development and persistence is poorly described. Here, we focused on the expression pattern of osteopontin (OPN), which is a well described cytokine, in MS brain tissue. Methods Autopsied brain sections from MS cases with and without B cell pathology were screened for the presence of CD20+ B cell aggregates and co-expression of OPN. To demonstrate the effect of OPN on B cells flow cytometry, ELISA and in vitro aggregation assays were conducted using peripheral blood of healthy volunteers. Results Although OPN was expressed in MS brain tissue independent of B cell pathology, it was also highly expressed within B cell aggregates. In vitro studies demonstrated that OPN downregulated the co-stimulatory molecules CD80 and CD86 on B cells. Furthermore, OPN-treated B cells produced significantly lower amounts of IL-6. However, OPN-treated B cells also exhibited a higher tendency to form homotypic cell aggregates in vitro. Conclusion Taken together, our data indicate a conflicting role of OPN in modulating B cell responses.