Expression and Reexpression of Recombination Activating Genes: Relevance to the Development of Autoimmune States

A bstract : Like all antibodies, autoreactive antibodies are generated in developing B cells in the bone marrow by variable (V), diversity (D), and joining (J) recombination under the regulation of recombination activating gene (RAG) 1 and RAG2 proteins. Deletion, anergy, and receptor edition prevent the emergence of autoreactive B cells. In the periphery, somatic hypermutation during the course of germinal center responses can lead to the emergence of autoreactive and low‐affinity antibody‐producing B cells. Deletion and receptor revision regulate autoreactive and inappropriate B cells. Defects in central or peripheral tolerance mechanisms associated with RAG expression could contribute to the appearance of autoreactive B cells. We demonstrate the presence of RAG + B cells in CD5‐expressing cells outside germinal centers. Our data suggest that receptor revision in the periphery also may occur in unusual sites when B cells are induced to express CD5. This revision may correspond to a novel regulation checkpoint in which impaired control of RAG expression could generate autoreactive B cells and lead to autoimmune states.