This application proposes the continuation of studies on somatic hypermutation of immunoglobulin (Ig) genes. During the previous funding period a connection between somatiC hypermutation and initiation of transcription was found, leading to a model of transcription coupled repair initiated by a specific mutator factor. Decisive experiments to test this model are proposed, most of them based on the use of transgenic mice carrying various test transgenes. These studies are important for the understanding of the creation of the varied repertoire of variable Ig genes with the potential of reaCting against any foreign antigenic determinant, including perhaps tumor cell antigens. Furthermore, somatic hypermutation has been implicated in autoimmune diseases. It is likely that understanding the components involved in somatic mutation will aid in understanding the genetic and environmental causes of autoimmunity.