Origin and diversity of pathogenic human monoclonal antibodies to the NMDA receptor

Anti–N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most common autoimmune encephalitis, where autoantibodies against the GluN1 subunit of the NMDAR disrupt normal neuronal signaling. While more is now understood about the pathogenic role of the autoantibodies, it is still unclear how the humoral autoimmune response is triggered, where the antibody-producing cells originate and develop, and whether individual autoantibodies differ in their pathogenic potential depending on their intrinsic properties. Here, we will investigate the origin of antibody-producing cells in tumor-associated and viral-infection associated NMDAR encephalitis by functional comparison of serum, tumor-derived, and cerebrospinal fluid-derived B cells at single-cell level, through single-cell immune repertoire sequencing, cell-based assays and passive transfer models.