B1 cells promote pancreas infiltration by autoreactive T cells.
The entry of autoreactive T cells into the pancreas is a critical checkpoint in the development of autoimmune diabetes. In this study, we identify a role for B1 cells in this process using the DO11 x RIP-mOVA mouse model. In transgenic mice with islet-specific T cells, but no B cells, T cells are primed in the pancreatic lymph node but fail to enter the pancreas. Reconstitution of the B1 cell population by adoptive transfer permits extensive T cell pancreas infiltration. Reconstituted B1 cells traffic to the pancreas and modify expression of adhesion molecules on pancreatic vasculature, notably VCAM-1. Despite substantial pancreas infiltration, islet destruction is minimal unless regulatory T cells are depleted. These data identify a role for B1 cells in permitting circulating islet-specific T cells to access their Ag-bearing tissue and emphasize the existence of multiple checkpoints to regulate autoimmune disease.
Ryan
Gemma A
GA
Medical Research Council Center for Immune Regulation, University of Birmingham Medical School, Birmingham, United Kingdom.
Wang
Chun Jing
CJ
Chamberlain
Jayne L
JL
Attridge
Kesley
K
Schmidt
Emily M
EM
Kenefeck
Rupert
R
Clough
Louise E
LE
Dunussi-Joannopoulos
Kyri
K
Toellner
Kai-Michael
KM
Walker
Lucy S K
LS
D019264:Adoptive Transfer; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology* / Q000637:transplantation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology* / Q000637:transplantation; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D007515:Islets of Langerhans / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D051381:Rats; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology
D019010:Vascular Cell Adhesion Molecule-1; D010047:Ovalbumin