{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:03:05Z","timestamp":1790758985628,"version":"4.1.0"},"reference-count":66,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2019,2,1]],"date-time":"2019-02-01T00:00:00Z","timestamp":1548979200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The classical pathway of complement (CP) can mediate C3 opsonization of Ags responsible for the costimulation and activation of cognate B lymphocytes. In this manner, the complement system acts as a bridge between the innate and adaptive immune systems critical for establishing a humoral response. However, aberrant complement activation is often observed in autoimmune diseases in which C3 deposition on self-antigens may serve to activate self-reactive B cell clones. In this study, we use BIVV009 (Sutimlimab), a clinical stage, humanized mAb that specifically inhibits the CP-specific serine protease C1s to evaluate the impact of upstream CP antagonism on activation and proliferation of normal and autoimmune human B cells. We report that BIVV009 significantly inhibited complement-mediated activation and proliferation of primary human B cells. Strikingly, CP antagonism suppressed human Ig\u2013induced activation of B cells derived from patients with rheumatoid arthritis. These results suggest that clinical use of CP inhibitors in autoimmune patients may not only block complement-mediated tissue damage, but may also prevent the long-term activation of autoimmune B cells and the production of autoantibodies that contribute to the underlying pathologic condition of these diseases.<\/jats:p>","DOI":"10.4049\/jimmunol.1800998","type":"journal-article","created":{"date-parts":[[2019,1,11]],"date-time":"2019-01-11T22:34:16Z","timestamp":1547246056000},"page":"1200-1209","source":"Crossref","is-referenced-by-count":30,"title":["C1s Inhibition by BIVV009 (Sutimlimab) Prevents Complement-Enhanced Activation of Autoimmune Human B Cells In Vitro"],"prefix":"10.1093","volume":"202","author":[{"given":"Pavel A","family":"Nikitin","sequence":"first","affiliation":[{"name":"Bioverativ, a Sanofi company , South San Francisco, CA 94080"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1442-4467","authenticated-orcid":false,"given":"Eileen L","family":"Rose","sequence":"additional","affiliation":[{"name":"Bioverativ, a Sanofi company , South San Francisco, CA 94080"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony S","family":"Byun","sequence":"additional","affiliation":[{"name":"Bioverativ, a Sanofi company , South San Francisco, CA 94080"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3009-4947","authenticated-orcid":false,"given":"Graham C","family":"Parry","sequence":"additional","affiliation":[{"name":"Bioverativ, a Sanofi company , South San Francisco, CA 94080"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7901-2730","authenticated-orcid":false,"given":"Sandip","family":"Panicker","sequence":"additional","affiliation":[{"name":"Bioverativ, a Sanofi company , South San Francisco, CA 94080"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,2,15]]},"reference":[{"key":"2025030417560761100_r1","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1038\/353765a0","article-title":"Elimination from peripheral lymphoid tissues of self-reactive B lymphocytes recognizing membrane-bound antigens","volume":"353","author":"Hartley","year":"1991","journal-title":"Nature"},{"key":"2025030417560761100_r2","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1038\/nri1939","article-title":"Receptor editing in lymphocyte development and central tolerance","volume":"6","author":"Nemazee","year":"2006","journal-title":"Nat. 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