Pathogenic Roles of Age-Associated B Cells in Neuromyelitis Optica Spectrum Disorder

Abstract

Age-associated B cells (ABCs), initially identified in aged mice, are a distinct B cell subset that plays crucial roles in autoimmune diseases through the production of autoantibodies, proinflammatory cytokines, and antigen presentation. Although a definitive set of markers for identifying ABCs has not yet been established, they are commonly characterized by the expression of CD11c, CD11b, and the transcription factor T-bet, along with reduced levels of CD21, either alone or in combination. ABC differentiation is driven by Toll-like receptor 7 (TLR7) signaling in conjunction with cytokines such as interleukin-21 (IL-21) and interferon-gamma (IFNγ). Importantly, ABCs expand in the blood or inflamed tissues and exhibit pathogenic functions in various autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome, Crohn's disease, axial spondyloarthritis, Grave's disease, and multiple sclerosis. Recently, ABCs have been implicated in neuromyelitis optica spectrum disorder (NMOSD), a chronic inflammatory astrocytopathy mediated by anti-AQP4 antibody-producing B cells characterized by relapses and remissions. In the acute phase, CD21^lo B cells can differentiate into anti-AQP4 antibody-producing cells and expand in both cerebrospinal fluid and blood. In the chronic phase, an increased frequency of CD11c^hi B cells in the blood correlates with chronic neurological damage or brain injury. T peripheral helper type 1 cells, which produce IFNγ and IL-21, may support ABC differentiation in both phases. This review explores the role of ABCs in NMOSD, highlighting key studies that link ABC subsets to disease pathology. Understanding ABC-mediated mechanisms in NMOSD may open avenues for novel therapeutic strategies.