Project R-15856

IgD-CD27- double negative (DN) B cells as drivers of antibody-mediated autoimmune diseases: Unraveling their role in autoimmune diseases targeting membrane receptors of the nervous system (Research)

In antibody-mediated autoimmune diseases targeting neuronal receptors and ion channels, the immune system aberrantly targets the nervous system, such as the peripheral nervous system in myasthenia gravis (MG). B cells and their progeny, plasma cells, are important immune cells contributing to autoimmunity by producing autoreactive antibodies that mark self-antigens for immune mediated destruction. While B cell-directed therapies are being tested or already in use, they carry risks such as increased susceptibility to infections and neoplasms and decreased vaccine responses. Targeting specific B cell subsets with pathological involvement may improve the risk-benefit ratio compared to current therapies. Increased levels of IgD-CD27- double negative (DN) B cells and their association with clinical characteristics suggest a pathological role of these cells in antibody-mediated neurological autoimmune diseases. This project aims to identify and validate diseaserelevant DN B cells in MG, serving as a model for such disorders. This increased insight into the pathogenic mechanisms of peripheral neurological disorders will bring us to the next step to study this also in central nervous system diseases. Furthermore, by advancing our understanding of DN B cells in the pathology of antibody-mediated autoimmune diseases, this research could pave the way for novel, more targeted therapeutic strategies.

01 October 2025 - 30 September 2029