Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
CD19+IgM+ cells demonstrate enhanced therapeutic efficacy in type 1 diabetes mellitus
Andrew D. Vonberg, … , Steven K. Lundy, Massimo Pietropaolo
Andrew D. Vonberg, … , Steven K. Lundy, Massimo Pietropaolo
Published December 6, 2018
Citation Information: JCI Insight. 2018;3(23):e99860. https://doi.org/10.1172/jci.insight.99860.
View: Text | PDF
Research Article Immunology

CD19+IgM+ cells demonstrate enhanced therapeutic efficacy in type 1 diabetes mellitus

  • Text
  • PDF
Abstract

We describe a protective effect on autoimmune diabetes and reduced destructive insulitis in NOD.scid recipients following splenocyte injections from diabetic NOD donors and sorted CD19+ cells compared with NOD.scid recipients receiving splenocytes alone. This protective effect was age specific (only CD19+ cells from young NOD donors exerted this effect; P < 0.001). We found that the CD19+IgM+ cell is the primary subpopulation of B cells that delayed transfer of diabetes mediated by diabetogenic T cells from NOD mice (P = 0.002). Removal of IgM+ cells from the CD19+ pool did not result in protection. Notably, protection conferred by CD19+IgM+ cotransfers were not dependent on the presence of Tregs, as their depletion did not affect their ability to delay onset of diabetes. Blockade of IL-10 with neutralizing antibodies at the time of CD19+ cell cotransfers also abrogated the therapeutic effect, suggesting that IL-10 secretion was an important component of protection. These results were strengthened by ex vivo incubation of CD19+ cells with IL-5, resulting in enhanced proliferation and IL-10 production and equivalently delayed diabetes progression (P = 0.0005). The potential to expand CD19+IgM+ cells, especially in response to IL-5 stimulation or by pharmacologic agents, may be a new therapeutic option for type 1 diabetes.

Authors

Andrew D. Vonberg, Maria Acevedo-Calado, Aaron R. Cox, Susan L. Pietropaolo, Roberto Gianani, Steven K. Lundy, Massimo Pietropaolo

×

Full Text PDF | Download (10.96 MB)


Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts