Identification of a novel role for matrix metalloproteinase-3 in the modulation of B cell responses in multiple sclerosis

Abstract

There has been a growing interest in the presence and role of B cell aggregates within the central nervous system of multiple sclerosis patients. However, very little is known about the expression profile of molecules associated with these aggregates and how they might be influencing aggregate development or persistence in the brain. The current study focuses on the effect of matrix metalloproteinase-3, which is associated with B cell aggregates in autopsied multiple sclerosis brain tissue, on B cells. Autopsied brain sections from multiple sclerosis cases and controls were screened for the presence of CD20⁺ B cell aggregates and expression of matrix metalloproteinase-3. Using flow cytometry, enzyme-linked immunosorbent assay and gene array as methods, in vitro studies were conducted using peripheral blood of healthy volunteers to demonstrate the effect of matrix metalloproteinase-3 on B cells. Autopsied brain sections from multiple sclerosis patients containing aggregates of B cells expressed a significantly higher amount of matrix metalloproteinase-3 compared to controls. In vitro experiments demonstrated that matrix metalloproteinase-3 dampened the overall activation status of B cells by downregulating CD69, CD80 and CD86. Furthermore, matrix metalloproteinase-3-treated B cells produced significantly lower amounts of interleukin-6. Gene array data confirmed that matrix metalloproteinase-3 altered the proliferation and survival profiles of B cells. Taken together, out data indicate a role for B cell modulatory properties of matrix metalloproteinase-3.

Keywords: B cells; central nervous system; immune modulation; matrix metalloproteinase-3; multiple sclerosis.