Enhanced trafficking to the pancreatic lymph nodes and auto-antigen presentation capacity distinguishes peritoneal B lymphocytes in non-obese diabetic mice

Alam, C.; Valkonen, S.; Ohls, S.; T�rnqvist, K.; H�nninen, A.

Abstract

<h4>Aims/hypothesis</h4>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.<h4>Methods</h4>The population dynamics, activation state, migratory behaviour and antigen presentation function were investigated in NOD peritoneal B cells.<h4>Results</h4>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.<h4>Conclusions/interpretation</h4>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.

Citation

Alam, C., Valkonen, S., Ohls, S., Törnqvist, K., & Hänninen, A. (2010). Enhanced trafficking to the pancreatic lymph nodes and auto-antigen presentation capacity distinguishes peritoneal B lymphocytes in non-obese diabetic mice. Diabetologia, 53, 346-355. https://doi.org/10.1007/s00125-009-1599-x

• Journal Article Type: Article
• Acceptance Date: Oct 23, 2009
• Online Publication Date: Nov 22, 2009
• Publication Date: 2010
• Deposit Date: May 26, 2022
• Journal: Diabetologia
• Print ISSN: 0012-186X
• Electronic ISSN: 1432-0428
• Publisher: Springer
• Peer Reviewed: Peer Reviewed
• Volume: 53
• Pages: 346-355
• DOI: https://doi.org/10.1007/s00125-009-1599-x
• Public URL: http://researchrepository.napier.ac.uk/Output/2870005