{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T03:31:31Z","timestamp":1789011091482,"version":"build-2803163510"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2016,12,1]],"date-time":"2016-12-01T00:00:00Z","timestamp":1480550400000},"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":[[2016,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Human IgG1 type I CD20 Abs, such as rituximab and ofatumumab (OFA), efficiently induce complement-dependent cytotoxicity (CDC) of CD20+ B cells by binding of C1 to hexamerized Fc domains. Unexpectedly, we found that type I CD20 Ab F(ab\u2032)2 fragments, as well as C1q-binding\u2013deficient IgG mutants, retained an ability to induce CDC, albeit with lower efficiency than for whole or unmodified IgG. Experiments using human serum depleted of specific complement components demonstrated that the observed lytic activity, which we termed \u201caccessory CDC,\u201d remained to be dependent on C1 and the classical pathway. We hypothesized that CD20 Ab-induced clustering of the IgM or IgG BCR was involved in accessory CDC. Indeed, accessory CDC was consistently observed in B cell lines expressing an IgM BCR and in some cell lines expressing an IgG BCR, but it was absent in BCR\u2212 B cell lines. A direct relationship between BCR expression and accessory CDC was established by transfecting the BCR into CD20+ cells: OFA-F(ab\u2032)2 fragments were able to induce CDC in the CD20+BCR+ cell population, but not in the CD20+BCR\u2212 population. Importantly, OFA-F(ab\u2032)2 fragments were able to induce CDC ex vivo in malignant B cells isolated from patients with mantle cell lymphoma and Waldenstr\u00f6m macroglobulinemia. In summary, accessory CDC represents a novel effector mechanism that is dependent on type I CD20 Ab\u2013induced BCR clustering. Accessory CDC may contribute to the excellent capacity of type I CD20 Abs to induce CDC, and thereby to the antitumor activity of such Abs in the clinic.<\/jats:p>","DOI":"10.4049\/jimmunol.1600811","type":"journal-article","created":{"date-parts":[[2016,11,3]],"date-time":"2016-11-03T02:03:34Z","timestamp":1478138614000},"page":"4829-4837","source":"Crossref","is-referenced-by-count":35,"title":["Type I CD20 Antibodies Recruit the B Cell Receptor for Complement-Dependent Lysis of Malignant B Cells"],"prefix":"10.1093","volume":"197","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6274-8554","authenticated-orcid":false,"given":"Patrick J","family":"Engelberts","sequence":"first","affiliation":[{"name":"Genmab , 3584 CM Utrecht,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marleen","family":"Voorhorst","sequence":"additional","affiliation":[{"name":"Genmab , 3584 CM Utrecht,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9738-9926","authenticated-orcid":false,"given":"Janine","family":"Schuurman","sequence":"additional","affiliation":[{"name":"Genmab , 3584 CM Utrecht,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5581-6950","authenticated-orcid":false,"given":"Tom","family":"van Meerten","sequence":"additional","affiliation":[{"name":"Department of Hematology, University Medical Center Groningen , 9713 GZ Groningen,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joost M","family":"Bakker","sequence":"additional","affiliation":[{"name":"Genmab , 3584 CM Utrecht,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6205-1733","authenticated-orcid":false,"given":"Tom","family":"Vink","sequence":"additional","affiliation":[{"name":"Genmab , 3584 CM Utrecht,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy J M","family":"Mackus","sequence":"additional","affiliation":[{"name":"Genmab , 3584 CM Utrecht,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5368-6849","authenticated-orcid":false,"given":"Esther C W","family":"Breij","sequence":"additional","affiliation":[{"name":"Genmab , 3584 CM Utrecht,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6142-5577","authenticated-orcid":false,"given":"Stefanie","family":"Derer","sequence":"additional","affiliation":[{"name":"Division of Stem Cell Transplantation and Immunotherapy, 2nd Department of Medicine, Christian Albrechts University , 24105 Kiel,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9181-8067","authenticated-orcid":false,"given":"Thomas","family":"Valerius","sequence":"additional","affiliation":[{"name":"Division of Stem Cell Transplantation and Immunotherapy, 2nd Department of Medicine, Christian Albrechts University , 24105 Kiel,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan G J","family":"van de Winkel","sequence":"additional","affiliation":[{"name":"Genmab , 3584 CM Utrecht,","place":["the Netherlands"]},{"name":"Department of Immunology, University Medical Center Utrecht , 3584 EA Utrecht,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4365-3859","authenticated-orcid":false,"given":"Paul W H I","family":"Parren","sequence":"additional","affiliation":[{"name":"Genmab , 3584 CM Utrecht,","place":["the Netherlands"]},{"name":"Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark , 5000 Odense,","place":["Denmark"]},{"name":"Department of Hematology and Blood Transfusion, Leiden University Medical Center , 2333 ZA Leiden,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7165-5771","authenticated-orcid":false,"given":"Frank J","family":"Beurskens","sequence":"additional","affiliation":[{"name":"Genmab , 3584 CM Utrecht,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,12,15]]},"reference":[{"key":"2025030618360756400_r1","doi-asserted-by":"crossref","first-page":"3525","DOI":"10.1200\/JCO.2010.27.9836","article-title":"Ofatumumab, a novel anti-CD20 monoclonal antibody for the treatment of B-cell malignancies","volume":"28","author":"Cheson","year":"2010","journal-title":"J. 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