The Importance of CD19+ Cells from Pre-diabetic NOD Mice in Delaying Onset of Disease in an Adoptive Transfer Model of Type 1 Diabetes Mellitus

CD19 cells;B cells in Type 1 Diabetes;Microbiology and Immunology;Health Sciences;Immunology

Vonberg, AndrewLundy, Steven K ;

University of Michigan

关键词: CD19 cells;    B cells in Type 1 Diabetes;    Microbiology and Immunology;    Health Sciences;    Immunology;   

Others  :  https://deepblue.lib.umich.edu/bitstream/handle/2027.42/137113/avonber_1.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

This dissertation describes a protective effect on autoimmune diabetes in NOD.scid recipients following injections of splenocytes from diabetic NOD donors in addition to purified CD19+ cells taken from pre-diabetic 6-week-old NOD female donors, compared to NOD.scid recipients receiving injections of splenocytes from diabetic NOD donors alone. Delayed progression of T1D was associated with a remarkable reduction in IL-1β plasma levels, a reduction in the severity of insulitis, and increased levels of CD19+ precursor B cells (compared to controls) likely exhibiting regulatory function upon activation and interaction with pathogenic T cells.The protective effect conferred by CD19+ cells was age specific as co-transfers of CD19+ cells from 6-week-old NOD mice exhibited a suppressive effect halting and/or significantly delaying the progression of diabetes and insulitis, while those from greater than 15-week-old NOD donors did not confer the same protective effect. Administration of a monoclonal antibody against IL-1β in NOD.scid recipients following injection of diabetic NOD splenocytes significantly delayed diabetes onset, unlike the administration of an isotype-matched antibody.In conclusion, progression to overt disease correlates with the pathogenic T cell’s escape from CD19+ cell–mediated regulation.These data provide evidence for a novel suppressive function of the regulatory B cell compartment in autoimmune diabetes.The expansion of regulatory CD19+ B cells may have therapeutic potential for T1D.