Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Lung inflammatory injury and tissue repair (Jul 2023)
    • Immune Environment in Glioblastoma (Feb 2023)
    • Korsmeyer Award 25th Anniversary Collection (Jan 2023)
    • Aging (Jul 2022)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Research letters
    • Letters to the editor
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Research letters
  • Letters to the editor
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
Treatment with CD20-specific antibody prevents and reverses autoimmune diabetes in mice
Chang-yun Hu, … , Mark J. Shlomchik, Li Wen
Chang-yun Hu, … , Mark J. Shlomchik, Li Wen
Published December 3, 2007
Citation Information: J Clin Invest. 2007;117(12):3857-3867. https://doi.org/10.1172/JCI32405.
View: Text | PDF
Research Article

Treatment with CD20-specific antibody prevents and reverses autoimmune diabetes in mice

  • Text
  • PDF
Abstract

The precise roles of B cells in promoting the pathogenesis of type 1 diabetes remain undefined. Here, we demonstrate that B cell depletion in mice can prevent or delay diabetes, reverse diabetes after frank hyperglycemia, and lead to the development of cells that suppress disease. To determine the efficacy and potential mechanism of therapeutic B cell depletion, we generated a transgenic NOD mouse expressing human CD20 (hCD20) on B cells. A single cycle of treatment with an antibody specific for hCD20 temporarily depleted B cells and significantly delayed and/or reduced the onset of diabetes. Furthermore, disease established to the point of clinical hyperglycemia could be reversed in over one-third of diabetic mice. Why B cell depletion is therapeutic for a variety of autoimmune diseases is unclear, although effects on antibodies, cytokines, and antigen presentation to T cells are thought to be important. In B cell–depleted NOD mice, we identified what we believe is a novel mechanism by which B cell depletion may lead to long-term remission through expansion of Tregs and regulatory B cells. Our results demonstrate clinical efficacy even in established disease and identify mechanisms for therapeutic action that will guide design and evaluation of parallel studies in patients.

Authors

Chang-yun Hu, Daniel Rodriguez-Pinto, Wei Du, Anupama Ahuja, Octavian Henegariu, F. Susan Wong, Mark J. Shlomchik, Li Wen

×

Figure 1

Phenotypic expression of transgenic hCD20 on B cells.

Options: View larger image (or click on image) Download as PowerPoint
Phenotypic expression of transgenic hCD20 on B cells.
(A) Splenocytes fr...
(A) Splenocytes from hCD20 mice were gated on B220+ B cells and stained with anti-hCD20 mAbs (2H7). All mature B cells expressed the transgenic hCD20. (B) Expression of hCD20 in BM cells of transgene-positive and control NOD mice. (C) Phenotypic characterization of hCD20 transgene-positive and control NOD mouse spleen cells. The splenocytes were gated on B220+ cells prior to analyzing for the different B cell markers.

Copyright © 2023 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts