Tolerance to self-antigen is necessary to prevent autoimmunity. In healthy individuals, self-reactive B cells are counter-selected or regulated However, in some individuals, failure in B cell tolerance checkpoints result in the formation of autoantibodies and the potential development of autoimmune diseases. These autoantibodies can be pathogenic with devastating consequences in autoimmune disease such as systemic lupus erythematosus, rheumatoid arthritis, or antiphospholipid syndrome. Understanding origin of self-reactivity, and more precisely autoreactive B cells, has therapeutic relevance. Indeed, depletion of B cells is often beneficial, but paradoxically, B cell targeting therapies are not always effective, as different type of B cells are maintaining the diseases: each autoimmune disease may have its own “unique B cell history”. The general aim of this project is to develop tools for the precise characterization of autoreactive B cells in multiple B-cell mediated autoimmune disease.
This study will develop methods and tools, and build a reference network for the study of autoreactive B cells in the Upper Rhine region and understand the role of autoreactive B cells in autoantibody mediated diseases and potentially address gaps in their management.