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Here, we used single\u2010cell full\u2010length RNA\u2010seq and BCR reconstruction to simultaneously assess the phenotypes, isotypes, constant region polymorphisms, and the paired heavy\u2010 and light\u2010chain repertoires in intrathecal B cells. We detected extensive clonal connections between the memory B cell and antibody\u2010secreting cell (ASC) compartments and observed clonally related cells of different isotypes including IgM\/IgG1, IgG1\/IgA1, IgG1\/IgG2, and IgM\/IgA1. There was a strong dominance of the G1m1 allotype constant region polymorphisms in ASCs, but not in memory B cells. Tightly linked to the G1m1 allotype, we found a preferential pairing of the immunoglobulin heavy\u2010chain variable (\n                    <jats:italic>IGHV)4<\/jats:italic>\n                    gene family with the \u03ba variable\n                    <jats:italic>(IGKV)1<\/jats:italic>\n                    gene family. The\n                    <jats:italic>IGHV4\u201039<\/jats:italic>\n                    gene was most used and showed the highest frequency of pairing with\n                    <jats:italic>IGKV1\u20105<\/jats:italic>\n                    and\n                    <jats:italic>IGKV1(D)\u201033<\/jats:italic>\n                    . These results link IgG constant region polymorphisms to stereotyped B\u2010cell responses in MS and indicate that the intrathecal B\u2010cell response in these patients could be directed against structurally similar epitopes.\n                  <\/jats:p>","DOI":"10.1002\/eji.202149576","type":"journal-article","created":{"date-parts":[[2022,1,29]],"date-time":"2022-01-29T20:43:07Z","timestamp":1643488987000},"page":"550-565","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Stereotyped B\u2010cell responses are linked to IgG constant region polymorphisms in multiple sclerosis"],"prefix":"10.1002","volume":"52","author":[{"given":"Ida","family":"Lindeman","sequence":"first","affiliation":[{"name":"Department of Immunology Oslo University Hospital  Oslo Norway"},{"name":"Department of Immunology Institute of Clinical Medicine University of Oslo  Oslo Norway"},{"name":"K.G. Jebsen Coeliac Disease Research Centre University of Oslo  Oslo Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justyna","family":"Polak","sequence":"additional","affiliation":[{"name":"Department of Immunology Institute of Clinical Medicine University of Oslo  Oslo Norway"},{"name":"K.G. Jebsen Coeliac Disease Research Centre University of Oslo  Oslo Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuo\u2010Wang","family":"Qiao","sequence":"additional","affiliation":[{"name":"Department of Immunology Oslo University Hospital  Oslo Norway"},{"name":"Department of Immunology Institute of Clinical Medicine University of Oslo  Oslo Norway"},{"name":"K.G. Jebsen Coeliac Disease Research Centre University of Oslo  Oslo Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Trygve","family":"Holm\u00f8y","sequence":"additional","affiliation":[{"name":"Department of Neurology Akershus University Hospital  L\u00f8renskog Norway"},{"name":"Department of Neurology Institute of Clinical Medicine University of Oslo  Oslo Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rune A.","family":"H\u00f8glund","sequence":"additional","affiliation":[{"name":"Department of Neurology Akershus University Hospital  L\u00f8renskog Norway"},{"name":"Department of Neurology Institute of Clinical Medicine University of Oslo  Oslo Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frode","family":"Vartdal","sequence":"additional","affiliation":[{"name":"Department of Immunology Institute of Clinical Medicine University of Oslo  Oslo Norway"},{"name":"K.G. 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Jebsen Coeliac Disease Research Centre University of Oslo  Oslo Norway"},{"name":"Department of Neurology Akershus University Hospital  L\u00f8renskog Norway"},{"name":"Department of Molecular Medicine Institute of Basic Medical Sciences University of Oslo  Oslo Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,2,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(48)90389-1"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2013.41"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410060205"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000008237"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1714"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2011.01.010"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI3568"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21641"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI63842"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2015.06.001"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.92724"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.5.2782"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awu205"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.9.6343"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.451"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.642"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2014.006"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-018-0082-3"},{"key":"e_1_2_9_20_1","first-page":"218","article-title":"Longevity, clonal relationship, and transcriptional program of celiac disease\u2010specific plasma cells","author":"Lindeman I.","year":"2021","journal-title":"J. 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