COMPETITION FOR FOLLICULAR NICHES EXCLUDES SELF-REACTIVE CELLS FROM THE RECIRCULATING B-CELL REPERTOIRE

Two different approaches to follow clones of B lymphocytes in a diverse preimmune repertoire reveal a new process for eliminating self-reactive cells in the periphery which depends on competition between cells with different specificities. A key feature of this censoring mechanism is the selective exclusion of self-antigen-binding B cells from the normal migration route into lymphoid follicles, resulting in their premature death. This is a striking example of homeostasis by cellular competition for limiting niches and may explain the paradoxical association between immunodeficiency and autoimmunity.