{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T13:10:48Z","timestamp":1789132248822,"version":"build-2803163510"},"reference-count":80,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2017,2,1]],"date-time":"2017-02-01T00:00:00Z","timestamp":1485907200000},"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":[[2017,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Myasthenia gravis (MG) is a prototypical B cell-mediated autoimmune disease affecting 20\u201350 people per 100,000. The majority of patients fall into two clinically distinguishable types based on whether they produce autoantibodies targeting the acetylcholine receptor (AChR-MG) or muscle specific kinase (MuSK-MG). The autoantibodies are pathogenic, but whether their generation is associated with broader defects in the B cell repertoire is unknown. To address this question, we performed deep sequencing of the BCR repertoire of AChR-MG, MuSK-MG, and healthy subjects to generate \u223c518,000 unique VH and VL sequences from sorted naive and memory B cell populations. AChR-MG and MuSK-MG subjects displayed distinct gene segment usage biases in both VH and VL sequences within the naive and memory compartments. The memory compartment of AChR-MG was further characterized by reduced positive selection of somatic mutations in the VH CDR and altered VH CDR3 physicochemical properties. The VL repertoire of MuSK-MG was specifically characterized by reduced V-J segment distance in recombined sequences, suggesting diminished VL receptor editing during B cell development. Our results identify large-scale abnormalities in both the naive and memory B cell repertoires. Particular abnormalities were unique to either AChR-MG or MuSK-MG, indicating that the repertoires reflect the distinct properties of the subtypes. These repertoire abnormalities are consistent with previously observed defects in B cell tolerance checkpoints in MG, thereby offering additional insight regarding the impact of tolerance defects on peripheral autoimmune repertoires. These collective findings point toward a deformed B cell repertoire as a fundamental component of MG.<\/jats:p>","DOI":"10.4049\/jimmunol.1601415","type":"journal-article","created":{"date-parts":[[2017,1,14]],"date-time":"2017-01-14T02:40:28Z","timestamp":1484361628000},"page":"1460-1473","source":"Crossref","is-referenced-by-count":108,"title":["Dysregulation of B Cell Repertoire Formation in Myasthenia Gravis Patients Revealed through Deep Sequencing"],"prefix":"10.1093","volume":"198","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1474-310X","authenticated-orcid":false,"given":"Jason A","family":"Vander Heiden","sequence":"first","affiliation":[{"name":"Interdepartmental Program in Computational Biology and Bioinformatics, Yale University , New Haven, CT 06511"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panos","family":"Stathopoulos","sequence":"additional","affiliation":[{"name":"Department of Neurology, Yale School of Medicine , New Haven, CT 06511"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9602-2092","authenticated-orcid":false,"given":"Julian Q","family":"Zhou","sequence":"additional","affiliation":[{"name":"Interdepartmental Program in Computational Biology and Bioinformatics, Yale University , New Haven, CT 06511"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luan","family":"Chen","sequence":"additional","affiliation":[{"name":"Interdepartmental Program in Computational Biology and Bioinformatics, Yale University , New Haven, CT 06511"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara J","family":"Gilbert","sequence":"additional","affiliation":[{"name":"AbVitro, Inc. , Boston, MA 02210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher R","family":"Bolen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Stanford University School of Medicine , Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0383-6845","authenticated-orcid":false,"given":"Richard J","family":"Barohn","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Kansas Medical Center , Kansas City, KS 66160"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7148-989X","authenticated-orcid":false,"given":"Mazen M","family":"Dimachkie","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Kansas Medical Center , Kansas City, KS 66160"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Ciafaloni","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Rochester School of Medicine , Rochester, NY 14642"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa J","family":"Broering","sequence":"additional","affiliation":[{"name":"AbVitro, Inc. , Boston, MA 02210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5634-5794","authenticated-orcid":false,"given":"Francois","family":"Vigneault","sequence":"additional","affiliation":[{"name":"AbVitro, Inc. , Boston, MA 02210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J","family":"Nowak","sequence":"additional","affiliation":[{"name":"Department of Neurology, Yale School of Medicine , New Haven, CT 06511"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven H","family":"Kleinstein","sequence":"additional","affiliation":[{"name":"Interdepartmental Program in Computational Biology and Bioinformatics, Yale University , New Haven, CT 06511"},{"name":"Department of Immunobiology, Yale School of Medicine , New Haven, CT 06511"},{"name":"Department of Pathology, Yale School of Medicine , New Haven, CT 06511"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7056-419X","authenticated-orcid":false,"given":"Kevin C","family":"O\u2019Connor","sequence":"additional","affiliation":[{"name":"Department of Neurology, Yale School of Medicine , New Haven, CT 06511"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,2,15]]},"reference":[{"key":"2025030615034745800_r1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jaut.2014.05.001","article-title":"Myasthenia gravis: paradox versus paradigm in autoimmunity","volume":"52","author":"Berrih-Aknin","year":"2014","journal-title":"J. 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