{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T09:31:23Z","timestamp":1786699883228,"version":"build-2736575974"},"reference-count":36,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The immune system is essential for protection against invading pathogens. However, if it fails to distinguish between non\u2010self (pathogens) and self, autoimmunity can result. B cells recognise pathogens using their B\u2010cell antigen receptor (BCR), a membrane\u2010bound antibody. The variable region of the BCR contacts antigens via complementarity\u2010determining regions (CDRs). This region is encoded by immunoglobulin (Ig) V(D)J gene segments, which are randomly recombined during B\u2010cell development. Failure to counter\u2010select unfavourable H\u2010CDR3s is considered an underlying feature of autoimmunity. Here, we examined the effect of impaired pre\u2010BCR selection on plasma cells (PCs) using a model of autoimmunity characterised by elevated serum autoantibody levels. Our results demonstrate that the absence of a pre\u2010BCR leads to an increase in H\u2010CDR3s that are translated into unfavourable reading frames, encoding highly hydrophobic and\/or basic amino acid residues, including a subset with extremely short H\u2010CDR3s. These features are not fully corrected by Ig light chains and persist in mature B cells. Ultimately resulting in the massive clonal expansion of PCs expressing a repertoire skewed towards extremely short H\u2010CDR3s that contain highly hydrophobic and\/or positively charged residues. Consequently, preB cells with unfavourable H\u2010CDR3 features lead to the expansion of autoreactive PCs with the same features.<\/jats:p>","DOI":"10.1002\/eji.70200","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T10:57:08Z","timestamp":1778151428000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Unfavourable H\u2010CDR3 Loops in preB Cells Lead to Highly Expanded Plasma Cell Clones"],"prefix":"10.1002","volume":"56","author":[{"given":"Alaitz","family":"Aranburu","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Inflammation Research Institute of Medicine, Sahlgrenska Academy, University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Engstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Inflammation Research Institute of Medicine, Sahlgrenska Academy, University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Demitz\u2010Helin","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Molecular Biology University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia M.","family":"Scheffler","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Inflammation Research Institute of Medicine, Sahlgrenska Academy, University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Camponeschi","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Inflammation Research Institute of Medicine, Sahlgrenska Academy, University of Gothenburg  Gothenburg Sweden"},{"name":"Department of Clinical Immunology and Transfusion Medicine Sahlgrenska University Hospital  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Sundell","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Inflammation Research Institute of Medicine, Sahlgrenska Academy, University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Inflammation Research Institute of Medicine, Sahlgrenska Academy, University of Gothenburg  Gothenburg Sweden"},{"name":"School of Life Sciences Jiangsu University  Zhenjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3415-0560","authenticated-orcid":false,"given":"Inga\u2010Lill","family":"M\u00e5rtensson","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Inflammation Research Institute of Medicine, Sahlgrenska Academy, University of Gothenburg  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