The role of T-cell B-cell interactions in germinal center reactions in Rheumatoid Arthritis

Abstract

The systemic autoimmune disease Rheumatoid Arthritis (RA) is marked by chronic inflammation of the synovium and subsequent joint damage. Although most RA patients show seropositivity for RA-associated auto-antibodies, such as anti-citrullinated protein antibodies or rheumatoid factor, a great variability in auto-antibodies is observed and various mechanisms of disease have been suggested. Approximately 30% of RA patients show formation of ectopic lymphoid organs in inflamed synovia. A correlation between the phenotypical structure of these ectopic lymphoid organs and enhanced auto-antibody production as well as disease severity is suggested by several studies. Although the latter two might be directly related, it raises the question whether lymphoid neogenesis contributes directly to RA pathology or is just a side-effect of local, chronic inflammation. It is generally accepted that the development and maturation of long-lived antibody-producing B-cells is predominantly regulated in lymphoid organs within specialized micro-environments, called germinal centers (GC). Several studies have demonstrated an association between disease severity, incidence and size of germinal centers, and various signaling pathways involved in T-/B-cell interactions. A recently identified subset of CD4+ helper T-cells, follicular helper T-cells (TFH) are thought to be the predominant helper T-cell subset involved in these T-/B-cell interactions in germinal centers. Therefore, this thesis will discuss present evidence to elucidate whether and how TFH B-cell help in germinal centers contributes to RA pathology.