| First Author | Bashratyan R | Year | 2013 |
| Journal | Eur J Immunol | Volume | 43 |
| Issue | 10 | Pages | 2588-97 |
| PubMed ID | 23817982 | Mgi Jnum | J:201680 |
| Mgi Id | MGI:5515267 | Doi | 10.1002/eji.201343376 |
| Citation | Bashratyan R, et al. (2013) Insulinoma-released exosomes activate autoreactive marginal zone-like B cells that expand endogenously in prediabetic NOD mice. Eur J Immunol 43(10):2588-97 |
| abstractText | Exosomes (EXOs) are nano-sized secreted microvesicles that can function as potent endogenous carriers of adjuvant and antigens. To examine a possible role in autoimmunity for EXOs, we studied EXO-induced immune responses in nonobese diabetic (NOD) mice, an autoimmune-prone strain with tissue-specific targeting at insulin-secreting beta cells. EXOs released by insulinoma cells can activate various antigen-presenting cells to secrete several proinflammatory cytokines and chemokines. A subset of B cells responded to EXO stimulation in culture by proliferation, and expressed surface markers representing marginal zone B cells, which was independent of T helper cells. Importantly, splenic B cells from prediabetic NOD mice, but not diabetic-resistant mice, exhibited increased reactivity to EXOs, which was correlated with a high level of serum EXOs. We found that MyD88-mediated innate TLR signals were essential for the B-cell response; transgenic B cells expressing surface immunoglobulin specific for insulin reacted to EXO stimulation, and addition of a calcineurin inhibitor FK506 abrogated the EXO-induced B-cell response, suggesting that both innate and antigen-specific signals may be involved. Thus, EXOs may contribute to the development of autoimmunity and type 1 diabetes in NOD mice, partially via activating autoreactive marginal zone-like B cells. |
