{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T08:34:27Z","timestamp":1791016467142,"version":"4.1.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2009,11,1]],"date-time":"2009-11-01T00:00:00Z","timestamp":1257033600000},"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":[[2009,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Type 1 diabetes results from T cell-mediated destruction of insulin-producing \u03b2 cells. Although elimination of B lymphocytes has proven successful at preventing disease, modulation of B cell function as a means to prevent type 1 diabetes has not been investigated. The development, fate, and function of B lymphocytes depend upon BCR signaling, which is mediated in part by Bruton\u2019s tyrosine kinase (BTK). When introduced into NOD mice, btk deficiency only modestly reduces B cell numbers, but dramatically protects against diabetes. In NOD, btk deficiency mirrors changes in B cell subsets seen in other strains, but also improves B cell-related tolerance, as indicated by failure to generate insulin autoantibodies. Introduction of an anti-insulin BCR H chain transgene restores diabetes in btk-deficient NOD mice, indicating that btk-deficient B cells are functionally capable of promoting autoimmune diabetes if they have a critical autoimmune specificity. This suggests that the disease-protective effect of btk deficiency may reflect a lack of autoreactive specificities in the B cell repertoire. Thus, signaling via BTK can be modulated to improve B cell tolerance, and prevent T cell-mediated autoimmune diabetes.<\/jats:p>","DOI":"10.4049\/jimmunol.0900367","type":"journal-article","created":{"date-parts":[[2009,10,20]],"date-time":"2009-10-20T01:31:56Z","timestamp":1256002316000},"page":"6403-6412","source":"Crossref","is-referenced-by-count":40,"title":["Reduced Diabetes in <i>btk<\/i>-Deficient Nonobese Diabetic Mice and Restoration of Diabetes with Provision of an Anti-Insulin IgH Chain Transgene"],"prefix":"10.1093","volume":"183","author":[{"given":"Peggy L","family":"Kendall","sequence":"first","affiliation":[{"name":"Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J","family":"Moore","sequence":"additional","affiliation":[{"name":"Pediatrics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chrys","family":"Hulbert","sequence":"additional","affiliation":[{"name":"Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen L","family":"Hoek","sequence":"additional","affiliation":[{"name":"Microbiology and Immunology, Vanderbilt University Medical Center , Nashville, TN 37212"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wasif N","family":"Khan","sequence":"additional","affiliation":[{"name":"Microbiology and Immunology, Vanderbilt University Medical Center , Nashville, TN 37212"},{"name":"Department of Microbiology and Immunology, Leonard Miller School of Medicine, University of Miami , Miami, FL 33136"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James W","family":"Thomas","sequence":"additional","affiliation":[{"name":"Medicine"},{"name":"Microbiology and Immunology, Vanderbilt University Medical Center , Nashville, TN 37212"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,11,15]]},"reference":[{"key":"2025032603221439400_R1","first-page":"269","article-title":"Aspects of the etiology, prediction, and prevention of insulin-dependent diabetes mellitus in childhood.","volume-title":"Pediatr. 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