{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T06:08:42Z","timestamp":1789538922532,"version":"build-2803163510"},"reference-count":105,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T00:00:00Z","timestamp":1755475200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012351","name":"Mitsubishi Tanabe Pharma Corporation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012351","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disorder of the central nervous system that predominantly affects the spinal cord and optic nerves. Aquaporin-4 antibodies have been identified as a distinguishing biomarker of NMOSD, allowing for differentiation from multiple sclerosis and other mimicking neurological conditions. Targeted monoclonal antibody treatments are evolving based on an improved understanding of the pathophysiology underlying NMOSD. Of particular influence is the idea that NMOSD is an autoantibody-mediated disease involving B cells. The hope is that targeted treatments will improve not only outcomes but also the impact and burden of the disease on patients. This review summarizes the latest evidence for B cell pathophysiology in NMOSD and highlights the cellular and molecular mechanisms of B cell-driven disease. Finally, we focus on the mechanisms of action of B cell-targeted therapies as they relate to the mechanisms of disease.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1635989","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T05:26:52Z","timestamp":1755494812000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["B cell depletion as a therapeutic strategy for neuromyelitis optica spectrum disorder: rationale, evidence, and challenges"],"prefix":"10.3389","volume":"16","author":[{"given":"Hirofumi","family":"Ochi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoru","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Nakahara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-10-8","article-title":"The history of neuromyelitis optica","volume":"10","author":"Jarius","year":"2013","journal-title":"J Neuroinflammation"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)17551-X","article-title":"A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis","volume":"364","author":"Lennon","year":"2004","journal-title":"Lancet"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20050304","article-title":"IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel","volume":"202","author":"Lennon","year":"2005","journal-title":"J Exp Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001729","article-title":"International consensus diagnostic criteria for neuromyelitis optica spectrum disorders","volume":"85","author":"Wingerchuk","year":"2015","journal-title":"Neurology"},{"key":"B5","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1111\/cen3.12107","article-title":"Evaluation of aquaporin-4 antibody assays","volume":"5","author":"Waters","year":"2014","journal-title":"Clin Exp Neuroimmunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1111\/ene.15239","article-title":"Late onset neuromyelitis optica spectrum disorder with anti-aquaporin 4 and anti-myelin oligodendrocyte glycoprotein antibodies","volume":"29","author":"Wang","year":"2022","journal-title":"Eur J Neurol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.nic.2016.12.010","article-title":"Neuromyelitis optica spectrum disorders","volume":"27","author":"Akaishi","year":"2017","journal-title":"Neuroimaging Clin N Am"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000101","article-title":"Distinction between MOG antibody-positive and AQP4 antibody-positive NMO spectrum disorders","volume":"82","author":"Sato","year":"2014","journal-title":"Neurology"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2021.103260","article-title":"Optic neuritis in Asian type opticospinal multiple sclerosis (OSMS-ON) in a non-Asian population: A functional-structural paradox","volume":"56","author":"Meneguette","year":"2021","journal-title":"Mult. 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