| First Author | Alam C | Year | 2010 |
| Journal | Diabetologia | Volume | 53 |
| Issue | 2 | Pages | 346-55 |
| PubMed ID | 20033667 | Mgi Jnum | J:156546 |
| Mgi Id | MGI:4420857 | Doi | 10.1007/s00125-009-1599-x |
| Citation | Alam C, et al. (2010) Enhanced trafficking to the pancreatic lymph nodes and auto-antigen presentation capacity distinguishes peritoneal B lymphocytes in non-obese diabetic mice. Diabetologia 53(2):346-55 |
| abstractText | AIMS/HYPOTHESIS: NOD.Igmicro ( null ) mice lacking mature B cells are highly resistant to diabetes and display poor CD4 T cell responses to autoantigens. Nevertheless, the degree to which different B cell subsets contribute to diabetes in NOD mice remains unresolved. Due to their role in the recognition of microbial and autoantigens, peritoneal B cell characteristics were examined in NOD mice to see if they differ developmentally, phenotypically or functionally in aspects relevant to diabetogenesis. METHODS: The population dynamics, activation state, migratory behaviour and antigen presentation function were investigated in NOD peritoneal B cells. RESULTS: NOD peritoneal B cells were found to express abnormally high levels of co-stimulatory molecules (CD40, CD86 and CD69). In contrast, the expression of L-selectin and integrin alpha4beta1 was markedly reduced in NOD mice compared with BALB/c and C57BL/6 mice. The number of B cells in the peritoneum was lower in NOD than in control mice throughout development; migration of B cells from the peritoneum to the pancreatic lymph nodes in NOD mice was enhanced tenfold. NOD B cells showed no chemotactic response to sphingosine-1-phosphate, which normally acts to retain B cells in the peritoneum. Peritoneal B cells of NOD mice also presented insulin autoantigen to CD4 T cells, inducing T cell proliferation. CONCLUSIONS/INTERPRETATION: NOD peritoneal B cells are hyperactivated, migrate to the pancreatic lymph nodes and are capable of driving insulin-specific CD4 T cell activation. These characteristics could make them important for inducing or amplifying T cell responses against islet-antigens. |
