Mia J Smith1, John C Cambier2, Peter A Gottlieb1. 1. Barbara Davis Center for Diabetes. 2. Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA.
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.
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.
Authors: H Noorchashm; Y K Lieu; N Noorchashm; S Y Rostami; S A Greeley; A Schlachterman; H K Song; L E Noto; A M Jevnikar; C F Barker; A Naji Journal: J Immunol Date: 1999-07-15 Impact factor: 5.422
Authors: Mia J Smith; Marynette Rihanek; Clive Wasserfall; Clayton E Mathews; Mark A Atkinson; Peter A Gottlieb; John C Cambier Journal: Diabetes Date: 2018-01-17 Impact factor: 9.461
Authors: Mark D Pescovitz; Carla J Greenbaum; Brian Bundy; Dorothy J Becker; Stephen E Gitelman; Robin Goland; Peter A Gottlieb; Jennifer B Marks; Antoinette Moran; Philip Raskin; Henry Rodriguez; Desmond A Schatz; Diane K Wherrett; Darrell M Wilson; Jeffrey P Krischer; Jay S Skyler Journal: Diabetes Care Date: 2013-09-11 Impact factor: 19.112