DIABETES AND ENDOCRINE PANCREAS II: Edited by Peter A. GottliebEndotypes in T1D: B lymphocytes and early onsetSmith, Mia J.a; Cambier, John C.b; Gottlieb, Peter A.aAuthor Information aBarbara Davis Center for Diabetes bDepartment of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA Correspondence to Mia J. Smith, DVM, PhD, 1775 Aurora Court, Barbara Davis Center for Diabetes, M20, Room 4107, Aurora, CO 80045-2537, USA. Tel: +1 303 724 9787; e-mail: mia.smith@CUAnschutz.edu Current Opinion in Endocrinology & Diabetes and Obesity: August 2020 - Volume 27 - Issue 4 - p 225-230 doi: 10.1097/MED.0000000000000547 Buy Metrics Abstract Purpose of review Although type 1 diabetes (T1D) is characterized by destruction of the pancreatic beta cells by self-reactive T cells, it has become increasingly evident that B cells also play a major role in disease development, likely functioning as antigen-presenting cells. Here we review the biology of islet antigen-reactive B cells and their participation in autoimmune diabetes. Recent findings Relative to late onset, individuals who develop T1D at an early age display increased accumulation of insulin-reactive B cells in islets. This B-cell signature is also associated with rapid progression of disease and responsiveness to B-cell depletion therapy. Also suggestive of B-cell participation in disease is loss of anergy in high-affinity insulin-reactive B cells. Importantly, loss of anergy is seen in patient's healthy first-degree relatives carrying certain T1D risk alleles, suggesting a role early in disease development. Summary Recent studies indicate that islet-reactive B cells may play a pathogenic role very early in T1D development in young patients, and suggest utility of therapies that target these cells. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.