B cells in rheumatoid arthritis

Despite intensive efforts we still have no clear idea regarding what induces inflammation in synovial membrane. This inflammation may result in hyperplasia of synoviocytes, infiltration of mononuclear cells, neoangiogenesis, pannus formation and finally joint destruction. One major problem in investigating the induction and progression of this chronic inflammation is that there is great heterogeneity from patient to patient in the appearance of the chronically inflamed synovial tissue (ST) [1]. One relatively constant feature, however, is the appearance of infiltrating lymphocytes in the majority of inflamed ST specimens [2,3]. These infiltrates are often diffuse and lack a distinct structural organization. Small clusters of T and B cells may be seen in the vicinity of the vasculature and plasma cells may accumulate in the inflamed tissue. In about 10% of the patients, though, the infiltrating lymphocytes become organized into large follicle-like structures, suggesting the development of so-called tertiary lymphoid tissue. The main cellular component in these structures is activated B cells, which can differentiate locally into plasma cells. Molecular analysis demonstrates that these B cells take part in an antigen-driven specific immune response in this ectopic lymphoid tissue [4,5,6]. The unresolved question is whether this is an autoimmune reaction directly related to the pathogenesis of rheumatoid arthritis (RA) or whether it is merely a bystander effect induced by the chronic inflammation. This review briefly describes our current knowledge of the immune processes that take place in the synovial membrane of patients with RA.The normal synovium is a relatively acellular structure, containing a thin lining layer of synoviocytes. The sublining is made up of an extracellular matrix in which blood vessels and a scattering of fat cells, fibroblasts and occasionally mononuclear cells are embedded. The picture is quite different for inflamed synovium of patients with R