| First Author | Shao WH | Year | 2008 |
| Journal | J Immunol | Volume | 180 |
| Issue | 11 | Pages | 7728-35 |
| PubMed ID | 18490777 | Mgi Jnum | J:136377 |
| Mgi Id | MGI:3796046 | Doi | 10.4049/jimmunol.180.11.7728 |
| Citation | Shao WH, et al. (2008) The Mer receptor tyrosine kinase is required for the loss of B cell tolerance in the chronic graft-versus-host disease model of systemic lupus erythematosus. J Immunol 180(11):7728-35 |
| abstractText | The Mer receptor tyrosine kinase mediates apoptotic cell phagocytosis and modulates macrophage cytokine production. Mer(-/-) mice have defective clearance of apoptotic debris and develop a systemic lupus erythematosus-like autoimmune syndrome. It was surprising then that B6-Mer(-/-) recipients of bm12 spleen cells failed to develop anti-dsDNA and anti-chromatin autoantibodies, whereas B6 hosts produced the expected autoimmune chronic graft-vs-host (cGVH) reaction. The lack of autoantibody formation in cGVH was not due to the failure of Mer-deficient hosts to provoke alloreactivity, because Mer(-/-) spleen cells were recognized by bm12 T cells in MLR. Cell transfer experiments in Rag-knockout mice indicated that the lack of autoantibody production in Mer(-/-) cGVH disease hosts was due to an intrinsic B cell defect. This defect did not cause a global inability to produce autoantibodies, because in vivo exposure to LPS stimulated production of autoantibodies in both B6 and Mer(-/-) mice. We further observed that wild-type B6 B cells up-regulated Mer upon activation in cGVH, and that B cells from mice lacking Mer showed a decreased up-regulation of activation-associated cell surface markers. These findings indicate that Mer serves an important role in the activation of self-reactive B cells in systemic autoimmunity. |
