Targeting CD22 reprograms b-cells and reverses autoimmune diabetes

Paolo Fiorina, Andrea Vergani, Shirine Dada, Mollie Jurewicz, Masie Wong, Kenneth Law, Erxi Wu, Ze Tian, Reza Abdi, Indira Guleria, Scott Rodig, Kyri Dunussi-Joannopoulos, Jeffrey Bluestone, Mohamed H. Sayegh

Research output: Contribution to journalArticle

Abstract

OBJECTIVES-To investigate a B-cell-depleting strategy to reverse diabetes in naive NOD mice. RESEARCH DESIGN AND METHODS-We targeted the CD22 receptor on B-cells of naive NOD mice to deplete and reprogram B-cells to effectively reverse autoimmune diabetes. RESULTS-Anti-CD22/cal monoclonal antibody (mAb) therapy resulted in early and prolonged B-cell depletion and delayed disease in pre-diabetic mice. Importantly, when new-onset hyperglycemic mice were treated with the anti-CD22/cal mAb, 100% of B-cell- depleted mice became normoglycemic by 2 days, and 70% of them maintained a state of long-term normoglycemia. Early therapy after onset of hyperglycemia and complete B-cell depletion are essential for optimal efficacy. Treated mice showed an increase in percentage of regulatory T-cells in islets and pancreatic lymph nodes and a diminished immune response to islet peptides in vitro. Transcriptome analysis of reemerging B-cells showed significant changes of a set of proinflammatory genes. Functionally, reemerging B-cells failed to present autoantigen and prevented diabetes when cotransferred with autoreactive CD4 + T-cells into NOD.SCID hosts. CONCLUSIONS-Targeting CD22 depletes and reprograms B- cells and reverses autoimmune diabetes, thereby providing a blueprint for development of novel therapies to cure autoimmune diabetes.

Original languageEnglish
Pages (from-to)3013-3024
Number of pages12
JournalDiabetes
Volume57
Issue number11
DOIs
Publication statusPublished - Nov 2008

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ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Fiorina, P., Vergani, A., Dada, S., Jurewicz, M., Wong, M., Law, K., Wu, E., Tian, Z., Abdi, R., Guleria, I., Rodig, S., Dunussi-Joannopoulos, K., Bluestone, J., & Sayegh, M. H. (2008). Targeting CD22 reprograms b-cells and reverses autoimmune diabetes. Diabetes, 57(11), 3013-3024. https://doi.org/10.2337/db08-0420