{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T18:42:29Z","timestamp":1761676949798,"version":"3.37.3"},"reference-count":56,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,2,16]],"date-time":"2021-02-16T00:00:00Z","timestamp":1613433600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010127","name":"J\u00fcrgen Manchot Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010127","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Infections with <jats:italic>Streptococcus pneumoniae<\/jats:italic> can cause severe diseases in humans including pneumonia. Although guidelines for vaccination have been established, <jats:italic>S. pneumoniae<\/jats:italic> is still responsible for a serious burden of disease around the globe. Currently, two pneumococcal immunizations are available, namely the pure polysaccharide vaccine Pneumovax23 (P23) and the conjugate\u2010vaccine Prevenar13 (PCV13). We recently reported impaired thymus\u2010independent antibody responses towards P23 in mice overexpressing the immunoinhibitory adapter SLy2. The purpose of this study was to evaluate adaptive B\u2010cell responses towards the thymus\u2010dependent vaccine PCV13 in SLy2\u2010overexpressing mice and to study their survival rate during pneumococcal lung infection. Moreover, we investigated B\u2010cell developmental stages within the bone marrow (BM) in the context of excessive SLy2\u2010expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>B\u2010cell subsets and their surface immune globulins were investigated by flow cytometry. For class\u2010switch assays, isolated splenic B cells were stimulated in vitro with lipopolysaccharide and interleukin\u20104 and antibody secretion was quantified via LEGENDplex. To study PCV13\u2010specific responses, mice were immunized and serum antibody titers (immunoglobulin M,\u00a0immunoglobulins IgG<jats:sub>1<\/jats:sub>, IgG<jats:sub>2<\/jats:sub>, and IgG<jats:sub>3<\/jats:sub>) were examined by enzyme\u2010linked immunosorbent assay. Survival rates of mice were assessed within 7 days upon intranasal challenge with <jats:italic>S. pneumoniae<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our data demonstrate impaired IgG<jats:sub>1<\/jats:sub> and IgG<jats:sub>3<\/jats:sub> antibody responses towards the pneumococcal conjugate\u2010vaccine PCV13 in SLy2\u2010overexpressing mice. This was accompanied by reduced frequencies and numbers of BM\u2010resident plasmablasts. In addition, we found drastically reduced counts of B\u2010cell precursors in the BM of SLy2\u2010Tg mice. The survival rate upon intranasal challenge with <jats:italic>S. pneumoniae<\/jats:italic> was mostly comparable between the genotypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings demonstrate an important role of the adapter protein SLy2 in the context of adaptive antibody responses against pneumococcal conjugate\u2010vaccine. Interestingly, deficits in humoral immunity seemed to be compensated by cellular immune effectors upon bacterial challenge. Our study further shows a novel relevance of SLy2 for plasmablasts and B\u2010cell progenitors in the BM.<\/jats:p><\/jats:sec>","DOI":"10.1002\/iid3.413","type":"journal-article","created":{"date-parts":[[2021,2,20]],"date-time":"2021-02-20T00:21:15Z","timestamp":1613780475000},"page":"533-546","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["SLy2\u2010overexpression impairs B\u2010cell development in the bone marrow and the IgG response towards pneumococcal conjugate\u2010vaccine"],"prefix":"10.1002","volume":"9","author":[{"given":"Jennifer","family":"Jaufmann","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Experimental Therapy and Toxicology, Institute of Experimental and Clinical Pharmacology and Pharmacogenomik and ICePhA University of Tuebingen  Tuebingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leyla","family":"T\u00fcmen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Experimental Therapy and Toxicology, Institute of Experimental and Clinical Pharmacology and Pharmacogenomik and ICePhA University of Tuebingen  Tuebingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6049-0257","authenticated-orcid":false,"given":"Sandra","family":"Beer\u2010Hammer","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Experimental Therapy and Toxicology, Institute of Experimental and Clinical Pharmacology and Pharmacogenomik and ICePhA University of Tuebingen  Tuebingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,2,16]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-018-0001-8"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/femsre\/fux037"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2016.1261772"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-019-03485-3"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.5863\/1551-6776-21.1.27"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2005.04.011"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201141890"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI8472"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-004-0182-2"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.4161\/hv.7.10.16794"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.201511-778FR"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201444882"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/iid3.365"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204698"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2010.05.004"},{"issue":"417","key":"e_1_2_11_17_1","article-title":"A breakpoint map of recurrent chromosomal rearrangements in human neoplasia","volume":"15","author":"Mitelman F","year":"1997","journal-title":"Nature Genet"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.155184"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20031816"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.09-140806"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1086\/520000"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35706"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2009.03890.x"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2005.07.022"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2010.00940.x"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201847517"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201747019"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.01.046"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2000.imr017510.x"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2901"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1700943"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1121632109"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1107172108"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3795"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3804"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.03.003"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3802"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000001816"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00520"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2511"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(02)00335-7"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(03)00267-X"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3348"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0025558"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.10.7043-7046.2005"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1701065"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2011.07.012"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.21.9646-9660.2005"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2172-10-38"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/35030112"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1454"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06159"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2003.11.008"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2011.06.012"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M008387200"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1159\/000095663"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320370742"}],"container-title":["Immunity, Inflammation and Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/iid3.413","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/iid3.413","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/iid3.413","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T04:57:03Z","timestamp":1692680223000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/iid3.413"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,16]]},"references-count":56,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["10.1002\/iid3.413"],"URL":"https:\/\/doi.org\/10.1002\/iid3.413","archive":["Portico"],"relation":{},"ISSN":["2050-4527","2050-4527"],"issn-type":[{"type":"print","value":"2050-4527"},{"type":"electronic","value":"2050-4527"}],"subject":[],"published":{"date-parts":[[2021,2,16]]},"assertion":[{"value":"2020-11-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}