The structure and origin of rheumatoid factors

The recently determined X-ray crystal structure of a human rheumatoid factor Fab bound to IgG Fe provides the basis of a new hypothesis for the origin of these autoantibodies in rheumatoid arthritis. The observation that Fe is bound outside the conventional antigen combining site suggests it novel form of crossreactivity with simultaneous binding of another antigen, potentiated by somatic mutation. This article discusses the implications for the induction of these autoantibodies.