A current paradigm for the pathogenesis of rheumatoid arthritis that does not require an immune-recognition event of arthritogenic antigens at the induction phase. In this paradigm, nonspecific inflammation from a variety of causes precipitates an aberrant synovial response in a genetically susceptible individual. Subsequent recruitment of immune cells, including B cells, T cells, and dendritic cells, establishes an ectopic lymphoid organ in the synovium that facilitates the local production of autoantibodies to synovial constituents. Autoantibodies, along with activated T cells, serve to amplify the inflammation and the consequent tissue damage. Such a nonspecific onset for the disease is in keeping with the observed heterogeneity in clinical, pathological, and immunological features of RA.