{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T19:20:43Z","timestamp":1777922443061,"version":"3.51.4"},"reference-count":35,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T00:00:00Z","timestamp":1569888000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Monoclonal Antibodies in Immunodiagnosis &amp; Immunotherapy"],"published-print":{"date-parts":[[2019,10,1]]},"abstract":"<jats:p>\n                    Type 1 diabetes mellitus is an autoimmune syndrome defined by the presence of autoreactive T and B cells, which results in destruction of insulin-producing beta cells. Autoantibodies against GAD65 (glutamic acid decarboxylase 65)\u2014a membrane-bound enzyme on pancreatic beta cells, contribute to beta cells' destruction and the loss of pancreatic functions. Mouse Fc\u03b3RIIb on B lymphocytes possesses an inhibitory effect on the activity of these cells. We hypothesized that it may be possible to suppress GAD65-specific B cells in mice with diabetes using chimeric molecules, containing an anti-Fc\u03b3RIIb antibody, coupled to peptide B\/T epitopes derived from the GAD65 protein. With these engineered chimeras, we expect to selectively co-cross-link the anti-GAD65-specific B cell receptor (BCR) and Fc\u03b3RIIb, thus delivering a suppressive signal to the targeted B cells. An anti-Fc\u03b3RIIb monoclonal antibody and two synthetic peptide epitopes derived from the GAD65 molecule were used for chimeras' construction. The suppressive activity of the engineered molecules was tested\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    in mice with streptozotocin (STZ)-induced type 1 diabetes. These chimeric molecules exclusively bind disease-associated B cells by recognizing their GAD65-specific BCR and selectively deliver a strong inhibitory signal through their surface Fc\u03b3RIIb receptors. A reduction in the number of anti-GAD65 IgG antibody-secreting plasmocytes and an increased percentage of apoptotic B lymphocytes were observed after treatment with protein-engineered antibodies of mice with STZ-induced type 1 diabetes.\n                  <\/jats:p>","DOI":"10.1089\/mab.2019.0030","type":"journal-article","created":{"date-parts":[[2019,10,11]],"date-time":"2019-10-11T16:48:00Z","timestamp":1570812480000},"page":"201-208","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Suppression of Disease-Associated B Lymphocytes by GAD65 Epitope-Carrying Protein-Engineered Molecules in a Streptozotocin-Induced Mouse Model of Diabetes"],"prefix":"10.1177","volume":"38","author":[{"given":"Iliyan Konstantinov","family":"Manoylov","sequence":"first","affiliation":[{"name":"Laboratory of Experimental Immunology, Stefan Angelov Institute of Microbiology, Bulgarian Academy of Sciences, Sofia, Bulgaria."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela Valentinova","family":"Boneva","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Immunology, Stefan Angelov Institute of Microbiology, Bulgarian Academy of Sciences, Sofia, Bulgaria."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irini Atanas","family":"Doytchinova","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Medical University of Sofia, Sofia, Bulgaria."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikolina Mihaylova","family":"Mihaylova","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Immunology, Stefan Angelov Institute of Microbiology, Bulgarian Academy of Sciences, Sofia, Bulgaria."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrey Ivanov","family":"Tchorbanov","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Immunology, Stefan Angelov Institute of Microbiology, Bulgarian Academy of Sciences, Sofia, Bulgaria."},{"name":"National Institute of Immunology, Sofia, Bulgaria."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2019,10,10]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3002102"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.26.11.3160"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/gene.2009.35"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12350"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2011.03.006"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1113954108"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2729"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.2337\/db08-1504"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2006.03244.x"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-005-1719-1"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.49.2.202"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(05)89002-9"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2005.11.010"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200737143"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2009.01.013"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2009.36"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2010.07.003"},{"key":"e_1_3_3_19_2","first-page":"356","article-title":"The streptozotocin-induced diabetic nude mouse model: Differences between animals from different sources","volume":"61","author":"Graham M","year":"2011","unstructured":"Graham M, , Janecek J, , Kittredge J, , Hering B, , and Schuurman H-J: The streptozotocin-induced diabetic nude mouse model: Differences between animals from different sources. 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