Poster Presentation The 13th International Congress of the Immunology of Diabetes Society 2013

Thymic B cells; new players in T1D progression? (#153)

Jennifer Smith 1 , Tamsin Zingerle Murray 1 , Allison Green 1
  1. York University, York, United Kingdom

Classically T cell development takes place in the thymus, whereas B cells develop in the bone marrow. Purging of autoreactive T and B cells takes place in their respective organs and is critical for preventing autoreactivity. Here we show, contrary to dogma, B cells develop in the thymus of NOD mice in an age-dependent manner. Using time-course studies in NOD, NOD-RAG-GFP mice (where newly developed B and T cells are identified as GFP positive) and control B6 miceĀ  we show that at 9 weeks of age B cells dramatically increase in the thymus of NOD mouse strains. This accumulation is preceded by a loss in T cell lineage commitment molecule c-kit in HSCs, and subsequent initiation of pro-B cell development. Thymic B cells have a distinct phenotype compared to peripheral splenic and peritoneal B cells, yet still have the capacity to form 'follicles' at the cortical/medullary junction. Flow cytometry studies demonstrate that follicular T helper-like cells accumulate in the thymus of NOD mice strains but not B6 mice and this is independent of the presence of mature B cells. Further, preliminary evidence suggests germinal centres form, promoting somatic hypermutation of thymic B cells. Following these unique events, B cells relocate to the medulla where they reside next to AIRE expressing medullary epithelial cells, and initial evdience suggests such relocation of B cells correlates with decreased absolute numbers of AIRE-mTECs. Importantly, these unique changes in the thymus of NOD mice occur prior to T1D detection. Our data highlights a potential new role for B cells in T1D development and warrants further investigations into the role thymic B cells may have in the shaping of the T cell repertoire to islet antigens.