{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T09:56:26Z","timestamp":1781344586855,"version":"3.54.1"},"posted":{"date-parts":[[2025,11,4]]},"group-title":"Immunology","reference-count":45,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"NCI","award":["P30CA016087"],"award-info":[{"award-number":["P30CA016087"]}]},{"name":"NCI","award":["R01CA243486"],"award-info":[{"award-number":["R01CA243486"]}]},{"name":"NIH","award":["T32AI100853"],"award-info":[{"award-number":["T32AI100853"]}]},{"name":"Genentech"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background and Objectives<\/jats:title>\n                  <jats:p>Patients with multiple sclerosis (pwMS) treated with ocrelizumab (OCR), a B-cell-depleting therapy, exhibit heterogeneous humoral responses to SARS-CoV-2 mRNA vaccination. The mechanisms underlying this variability remain incompletely understood. We performed a longitudinal analysis of B-cell subset dynamics and antigen-specific T cell responses in OCR-treated pwMS and healthy controls to determine how immune cell composition, timing of OCR infusion, and lymphocyte dynamics influence humoral response outcomes.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Based on post-vaccination anti-Spike IgG titers measured by multiplex bead immunoassay, pwMS were categorized as super-responders (SR), responders (R), or non-responders (NR). A 35-marker spectral flow cytometry panel was used to characterize T- and B-cell subsets longitudinally, at baseline and following stimulation with a SARS-CoV-2 peptide pool.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell populations were preserved across OCR-treated pwMS, and SARS-CoV-2-specific T cells remained detectable for more than 6 months after vaccination. In contrast, residual B-cell subset composition distinguished responders from non-responders. DN2-like B cells (CD19\n                    <jats:sup>+<\/jats:sup>\n                    CD27-IgD-T-bet\n                    <jats:sup>+<\/jats:sup>\n                    CD11c\n                    <jats:sup>+<\/jats:sup>\n                    CXCR5-) persisted despite repeated OCR infusions and were enriched in SR compared with NR. Repletion of mature na\u00efve B cells in peripheral blood correlated with time since last OCR infusion and with stronger humoral immune responses.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>B-cell subsets that resist OCR-mediated depletion may contribute to vaccine responsiveness in OCR-treated pwMS. Altered repletion kinetics of na\u00efve B cell subsets in non-responders suggest that specific B-cell populations may serve as predictive biomarkers of vaccine-induced humoral immunity, despite preserved T-cell responses.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.11.03.686372","type":"posted-content","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T02:05:22Z","timestamp":1762308322000},"source":"Crossref","is-referenced-by-count":0,"title":["Atypical memory B cells contribute to heterogeneous vaccine responses in ocrelizumab-treated patients with multiple sclerosis"],"prefix":"10.64898","author":[{"given":"Ryan","family":"Curtin","sequence":"first","affiliation":[{"name":"New York University (NYU) Grossman School of Medicine, New York, NY, USA"},{"name":"Department of Pathology, NYU Grossman School of Medicine, New York, NY, 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Vaccine Center and Department of Medicine, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Mulligan","sequence":"additional","affiliation":[{"name":"NYU Langone Vaccine Center and Department of Medicine, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Priest","sequence":"additional","affiliation":[{"name":"Genentech, Inc., South San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Cabatingan","sequence":"additional","affiliation":[{"name":"Genentech, Inc., South San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan C.","family":"Winger","sequence":"additional","affiliation":[{"name":"Genentech, Inc., South San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yury","family":"Patskovsky","sequence":"additional","affiliation":[{"name":"New York University (NYU) 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