[Frontiers in Bioscience 12, 2159-2170, January 1, 2007] 2159 Role of B cells in Sjögren´s syndrome - from benign lymphoproliferation to overt malignancy Roland Jonsson 1,2,3 , Elisabeth Nginamau 1 , Ewa Szyszko 1 , Karl A. Brokstad 1,3 1 Broegelmann Research Laboratory, The Gade Institute, University of Bergen, 2 Department of Rheumatology Haukeland University Hospital, Bergen, Norway, 3 Otolaryngology/Head and Neck Surgery, Haukeland University Hospital, Bergen, Norway TABLE OF CONTENTS 1. Abstract 2. Introduction 3. Characteristics of human B cells 4. The lymphoepithelial lesion and germinal centers in Sjögren’s syndrome 5. Autoantibodies in diagnosis and pathogenesis 6. Monoclonality and lymphoma 7. Long-lived plasma cells in Sjögren’s syndrome 8. B cell depletion in Sjögren’s syndrome 9. Concluding remarks 10. Acknowledgements 11. References 1. ABSTRACT The classical view of B cell biology is that these cells respond to foreign and self antigens and in this way promote protection, primarily by production of antibodies. However, recent studies suggest that B cells have diverse functions within the immune system other than antibody production, which could contribute to autoimmunity. This involves organization of lymphoid tissue, regulation of dendritic cells, antigen presentation, activation of T cells and production of cytokines. Both abnormalities in the distribution of B cell subsets, and recent discovery of clinical benefit after B cell depletion highlight the pivotal role of B cells in autoimmunity. This change in view of the role of B cells will be exemplified in one autoimmune disease namely Sjögren’s syndrome. 2. INTRODUCTION Sjögren’s syndrome is a chronic inflammatory and lymphoproliferative disease with autoimmune features characterized by a progressive mononuclear cell infiltration of exocrine glands, notably the lacrimal and salivary glands (autoimmune exocrinopathy). These lymphoid infiltrations may be followed by dryness of the eyes (keratoconjunctivitis sicca), dryness of the mouth (xerostomia), and frequently, dryness of the nose, throat, vagina, and skin (1). The spectrum of the disease extends from an organ-specific autoimmune disorder to a systemic process (musculoskeletal, pulmonary, gastric, hematologic, dermatologic, renal, and nervous system involvement).