Meningeal lymphoid hubs support antiviral and autoreactive immune responses 3987

Abstract Description There is growing interest in how immune cells in the meninges, membranes surrounding the brain and spinal cord, contribute to CNS homeostasis and disease. The dura mater, the outermost layer, houses innate and adaptive immune cells and serves as a site for B cell development. Recently, we identified lymphoid architecture surrounding a fenestrated venous plexus at the rostral-rhinal confluence of sinuses, termed the rostral-rhinal venolymphatic hub (hub). It exhibits intricate immune organization, including lymphatic vessels, and scRNA sequencing revealed that a diverse innate and adaptive immune cells inhabits this structure during homeostasis. Here, we show in response to an intranasal virus infection that the hub supports local germinal center (GC) reactions consisting of T follicular helper (Tfh) cells and GC B cells that undergo proliferation, class switch, and somatic hypermutation. In addition, we demonstrate that the hub can support autoimmune reactions against CNS antigens, such as myelin debris, that preferentially accumulates in this location. During development of autoimmunity, myelin oligodendrocyte glycoprotein (MOG)-reactive CD4+ T cells localize preferentially to the hub, interact with B cells, proliferate, and convert into Tfh cells. These data highlight how dural lymphoid architecture surrounding a vascular plexus sample both foreign- and self-antigens, leading to immunity that either protects (antiviral) or harms (autoimmune) the underlying CNS parenchyma. Funding Sources Supported by NINDS/NIH Topic Categories Neuroimmunology (NEUR)