title: Targeting CD22 reprograms B-cells and reverses autoimmune diabetes.
abstract: OBJECTIVE
  To investigate a B-cell-depleting strategy to reverse diabetes in naïve NOD mice.
  
  
  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.
authors.affiliation: Transplantation Research Center, Children's Hospital and Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Paolo
authors.initials: P
authors.lastname: Fiorina
authors.forename: Andrea
authors.initials: A
authors.lastname: Vergani
authors.forename: Shirine
authors.initials: S
authors.lastname: Dada
authors.forename: Mollie
authors.initials: M
authors.lastname: Jurewicz
authors.forename: Masie
authors.initials: M
authors.lastname: Wong
authors.forename: Kenneth
authors.initials: K
authors.lastname: Law
authors.forename: Erxi
authors.initials: E
authors.lastname: Wu
authors.forename: Ze
authors.initials: Z
authors.lastname: Tian
authors.forename: Reza
authors.initials: R
authors.lastname: Abdi
authors.forename: Indira
authors.initials: I
authors.lastname: Guleria
authors.forename: Scott
authors.initials: S
authors.lastname: Rodig
authors.forename: Kyri
authors.initials: K
authors.lastname: Dunussi-Joannopoulos
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Bluestone
authors.forename: Mohamed H
authors.initials: MH
authors.lastname: Sayegh
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D010179:Pancreas / Q000187:drug effects / Q000276:immunology; D011236:Prediabetic State / Q000276:immunology*; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D051918:Sialic Acid Binding Ig-like Lectin 2