Targeting CD22 Reprograms B-Cells and Reverses Autoimmune Diabetes

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Targeting CD22 Reprograms B-Cells and Reverses Autoimmune Diabetes

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Title: Targeting CD22 Reprograms B-Cells and Reverses Autoimmune Diabetes
Author: Dada, Shirine; Wong, Masie; Law, Kenneth; Wu, Erxi; Dunussi-Joannopoulos, Kyri; Bluestone, Jeffrey; Fiorina, Paolo; Vergani, Andrea; Jurewicz, Mollie; Tian, Ze; Abdi, Reza; Guleria, Indira; Rodig, Scott J.; Sayegh, Mohamed Hassan

Note: Order does not necessarily reflect citation order of authors.

Citation: Fiorina, Paolo, Andrea Vergani, Shirine Dada, Mollie Jurewicz, Masie Wong, Kenneth Law, Erxi Wu, et al. 2008. Targeting CD22 reprograms B-cells and reverses autoimmune diabetes. Diabetes 57(11): 3013-3024.
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Abstract: OBJECTIVES—To investigate a B-cell–depleting strategy to reverse diabetes in naïve NOD mice. RESEARCH DESIGN AND METHODS—We targeted the CD22 receptor on B-cells of naïve 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.
Published Version: doi:10.2337/db08-0420
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