Infection with a bacterium or virus induces the production of antibodies, specialised protein molecules that bind to and eliminate the microorganism. These antibodies are produced by B-cells that are stimulated by antigen (any foreign protein or carbohydrate) in the lymph nodes and spleen. During this process, they diversify their variable region genes (V-genes), encoding the antigen-binding region of the antibody, by switching on machinery that mutates the V-genes at a very high rate (somatic hypermutation). In autoimmune diseases, B-cells produce autoantibodies against self-antigens present on the patient's own tissues. Clusters of B- and T-cells are frequently found in the target organs of autoimmune disease. The aim of the work described here was to determine whether these clusters of cells are responding to stimulation by antigen. For this purpose we investigated the B-cell response in patients with an autoimmune disease affecting the salivary and lachrymal glands. By cloning and sequencing the expressed V-genes from indvidual clusters of cells in the salivary glands, we were able to show that the B-cells in these clusters are undergoing clonal proliferation, somatic hypermutation and antigen selection. The presence of similar structures in the target tissues of other autoimmune diseases suggests that this is a widespread phenomenon
