| Autor: |
van den Broek T; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA., Oleinika K; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA., Rahmayanti S; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA., Castrillon C; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA., van der Poel CE; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA., Carroll MC; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA. |
| Abstrakt: |
In autoreactive germinal centers (GC) initiated by a single rogue B cell clone, wild-type B cells expand and give rise to clones that target other autoantigens, known as epitope spreading. The chronic, progressive nature of epitope spreading calls for early interventions to limit autoimmune pathologies, but the kinetics and molecular requirements for wild-type B cell invasion and participation in GC remain largely unknown. With parabiosis and adoptive transfer approaches in a murine model of systemic lupus erythematosus, we demonstrate that wild-type B cells join existing GCs rapidly, clonally expand, persist, and contribute to autoantibody production and diversification. The invasion of autoreactive GCs by wild-type B cells required TLR7, B cell receptor specificity, antigen presentation, and type I interferon signaling. The adoptive transfer model provides a tool for identifying early events in the breaking of B cell tolerance in autoimmunity. |
