{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:03:14Z","timestamp":1790834594640,"version":"4.1.0"},"reference-count":62,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2015,6,1]],"date-time":"2015-06-01T00:00:00Z","timestamp":1433116800000},"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":[[2015,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Polymorphisms in the B lymphoid tyrosine kinase (BLK) gene have been associated with autoimmune diseases, including systemic lupus erythematosus, with risk correlating with reduced expression of BLK. How reduced expression of BLK causes autoimmunity is unknown. Using Blk+\/+, Blk+\/\u2212, and Blk\u2212\/\u2212 mice, we show that aged female Blk+\/\u2212 and Blk\u2212\/\u2212 mice produced higher anti-dsDNA IgG Abs and developed immune complex\u2013mediated glomerulonephritis, compared with Blk+\/+ mice. Starting at young age, Blk+\/\u2212 and Blk\u2212\/\u2212 mice accumulated increased numbers of splenic B1a cells, which differentiated into class-switched CD138+ IgG-secreting B1a cells. Increased infiltration of B1a-like cells into the kidneys was also observed in aged Blk+\/\u2212 and Blk\u2212\/\u2212 mice. In humans, we found that healthy individuals had BLK genotype-dependent levels of anti-dsDNA IgG Abs as well as increased numbers of a B1-like cell population, CD19+CD3\u2212CD20+CD43+CD27+, in peripheral blood. Furthermore, we describe the presence of B1-like cells in the tubulointerstitial space of human lupus kidney biopsies. Taken together, our study reveals a previously unappreciated role of reduced BLK expression on extraperitoneal accumulation of B1a cells in mice, as well as the presence of IgG autoantibodies and B1-like cells in humans.<\/jats:p>","DOI":"10.4049\/jimmunol.1402736","type":"journal-article","created":{"date-parts":[[2015,5,14]],"date-time":"2015-05-14T02:42:37Z","timestamp":1431571357000},"page":"5692-5702","source":"Crossref","is-referenced-by-count":48,"title":["Concordance of Increased B1 Cell Subset and Lupus Phenotypes in Mice and Humans Is Dependent on BLK Expression Levels"],"prefix":"10.1093","volume":"194","author":[{"given":"Ying-Yu","family":"Wu","sequence":"first","affiliation":[{"name":"Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation , Oklahoma City, OK 73104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ina","family":"Georg","sequence":"additional","affiliation":[{"name":"Centre for Genomics and Oncological Research (GENYO), Pfizer\u2013University of Granada\u2013Andalusian Regional Government, Health Sciences Technology Park , Granada 18016 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"D\u00edaz-Barreiro","sequence":"additional","affiliation":[{"name":"Centre for Genomics and Oncological Research (GENYO), Pfizer\u2013University of Granada\u2013Andalusian Regional Government, Health Sciences Technology Park , Granada 18016 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nieves","family":"Varela","sequence":"additional","affiliation":[{"name":"Centre for Genomics and Oncological Research (GENYO), Pfizer\u2013University of Granada\u2013Andalusian Regional Government, Health Sciences Technology Park , Granada 18016 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Lauwerys","sequence":"additional","affiliation":[{"name":"P\u00f4le de Pathologies Rhumatismales, Institut de Recherche Exp\u00e9rimentale et Clinique, Universit\u00e9 Catholique de Louvain , 1200 Brussels ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramesh","family":"Kumar","sequence":"additional","affiliation":[{"name":"Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation , Oklahoma City, OK 73104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harini","family":"Bagavant","sequence":"additional","affiliation":[{"name":"Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation , Oklahoma City, OK 73104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mireia","family":"Castillo-Mart\u00edn","sequence":"additional","affiliation":[{"name":"Department of Pathology, Icahn School of Medicine at Mount Sinai , New York, NY 10029"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fadi","family":"El Salem","sequence":"additional","affiliation":[{"name":"Department of Pathology, Icahn School of Medicine at Mount Sinai , New York, NY 10029"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7827-6301","authenticated-orcid":false,"given":"Concepci\u00f3n","family":"Mara\u00f1\u00f3n","sequence":"additional","affiliation":[{"name":"Centre for Genomics and Oncological Research (GENYO), Pfizer\u2013University of Granada\u2013Andalusian Regional Government, Health Sciences Technology Park , Granada 18016 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7632-4154","authenticated-orcid":false,"given":"Marta E","family":"Alarc\u00f3n-Riquelme","sequence":"additional","affiliation":[{"name":"Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation , Oklahoma City, OK 73104"},{"name":"Centre for Genomics and Oncological Research (GENYO), Pfizer\u2013University of Granada\u2013Andalusian Regional Government, Health Sciences Technology Park , Granada 18016 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,6,15]]},"reference":[{"key":"2025030706552129000_r1","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1016\/j.coi.2010.09.002","article-title":"Recent findings on genetics of systemic autoimmune diseases","volume":"22","author":"Delgado-Vega","year":"2010","journal-title":"Curr. 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