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
Year: 2017
Type: dissertation
Abstract: 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.
Author: Andrew D. Vonberg
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2748228600