Peritoneal B cells govern the outcome of diabetes in non-obese diabetic mice.

Type 1 diabetes mellitus (T1DM) results from autoimmune destruction of insulin-producing beta cells in the pancreatic islets. Although T1DM is mediated by T lymphocytes, B lymphocytes are essential for insulitis and disease progression in the non-obese diabetic mouse model. We find that B cells invading the pancreas phenotypically resemble B1a B cells in the peritoneal cavity, including the presence of CD5+. To investigate the link between the peritoneal cavity and lymphocytes invading the pancreas, we used intraperitoneal hypotonic lysis to target these cells. B1a cells were eliminated from the peritoneal compartment by this treatment and were quickly replaced by B2 cells. Both B1a and B2 B cells were concordantly redistributed away from insulitis lesions, while pancreatic T cells showed little change. As a consequence of these events, the onset of diabetes was significantly delayed. These findings indicate that simple perturbations of the B cell-enriched peritoneal compartment can affect the disease process in the pancreas even after islet invasion has begun.