B Cell Compartmental Features and Molecular Basis for Therapy in Neuromyelitis Optica Spectrum Disorder
Abstract
Background:
To characterize B cell programming towards autoimmunity across different compartments in patients with neuromyelitis optica spectrum disorder (NMOSD).
Methods:
We characterized B cell transcriptomic profiles via single-cell RNA sequencing across the blood, bone marrow and cerebrospinal fluid (CSF) in patients with NMOSD.
Results:
Four major subpopulations of B cells with distinct signatures across the tissues were identified: naïve B cells, memory B cells, autoimmune B cells, and antibody secreting cells (ASCs). NMOSD B cells show proinflammatory activity with an increased expression of chemokine receptor genes (CXCR3 and CXCR4). Blood B cells display an increase of antigen presentation markers (CD40 and CD83), as well as activation signatures (FOS, CD69 and JUN). In contrast, bone marrow contains a large ASCs pool with increased oxidative and metabolic activity reflected by COX genes and ATP synthase genes. Typically, NMOSD B cells become hyper-responsive to type I interferon, which facilitates B cell maturation and anti-aquaporin-4 autoantibody production. The fraction of antibody secreting cells (ASCs) was significantly elevated in NMOSD. Both CD19- and CD19+ ASCs could be ablated by tocilizumab but not rituximab treatment in NMOSD.
Conclusion:
B cells are compartmentally fine-tuned towards autoreactivity in NMOSD. Inhibition of type I interferon pathway may provide a new therapeutic avenue for NMOSD.
