{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T05:23:48Z","timestamp":1784784228406,"version":"3.55.0"},"reference-count":42,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T00:00:00Z","timestamp":1754611200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Ocrelizumab (OCR), a humanized anti\u2010CD20 monoclonal antibody, is highly efficient in relapsing\u2013remitting multiple sclerosis (RR\u2010MS). We assessed early cellular B\u2010cell profiles in patients prior to OCR treatment, on OCR treatment, and after 15\u2009months of therapy discontinuation. This study aims to provide new clues about the mechanisms of action of OCR and about disease pathophysiology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients with early, treatment\u2010naive, RR\u2010MS were included from 11 centers participating in an ancillary study of the ENSEMBLE trial (NCT03085810) to evaluate the effectiveness and safety of OCR. The phenotypic B\u2010cell immune profile was comprehensively assessed in 18 patients by spectral flow cytometry at baseline, after 1\u2009year of OCR treatment, and compared with 10 healthy volunteers (HVs) (matched for age and sex) on cryopreserved peripheral blood mononuclear cells (PBMC). We also analyzed B\u2010cell reconstitution after a median time of 15\u2009months after trial withdrawal in three patients by flow cytometry and single\u2010cell RNA sequencing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Using spectral flow cytometry we defined the proportions and absolute numbers of naive, transitional, Ig\u2010G, Ig\u2010A, Ig\u2010M memory B cells, Ig\u2010G, Ig\u2010A, Ig\u2010M plasmablasts, and plasma cells. At baseline we found an increased frequency of IgG\u2010secreting B cells in MS patients compared to HV. During OCR treatment, the proportion of the different subsets of B cells was strongly modified. In the mature clusters, we observed that the treatment partially spared memory IgA B cells. In parallel, we observed that differentiated IgA plasmablasts and plasma cells were more increased than the other differentiated clusters. Interestingly, in the three patients who stopped the treatment single\u2010cell RNA sequencing showed that the B cells that reappeared were mainly naive with an inflammatory and migratory phenotype concomitantly to a rise of regulatory B cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Our findings support an increased regulatory phenotype of remaining B cells under treatment with OCR and replenishment of undifferentiated B cells accumulating features of inflammatory and migratory patterns after OCR discontinuation, counterbalanced by an increased proportion of regulatory B cells.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.70135","type":"journal-article","created":{"date-parts":[[2025,8,9]],"date-time":"2025-08-09T02:59:34Z","timestamp":1754708374000},"page":"2271-2285","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Durable B\u2010Cell Impairment While Sparing\n                    <scp>IgA<\/scp>\n                    B Cells After Ocrelizumab Therapy in Multiple Sclerosis"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3031-5199","authenticated-orcid":false,"given":"Alexandra","family":"Garcia","sequence":"first","affiliation":[{"name":"INSERM, Center for Research in Transplantation and Translational Immunology CR2TI, UMR 1064 CHU Nantes, Nantes Universit\u00e9  Nantes 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