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* Department of Medicine, Division of Rheumatology, University of Pennsylvania, Philadelphia, PA 19104; and
Philadelphia Veterans Administration Medical Center, Philadelphia, PA 19104
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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by grants from the Alliance for Lupus Research, the Lupus Research Institute, the Lupus Foundation of South Jersey, the U.S. Department of Veterans Affairs, and the National Institutes of Health (DE017590, R01AR34156, and AI063626). P.L.C. is a scholar of the Mary Kirkland Lupus Foundation, which provided support for W-H.S.
2 Address correspondence and reprint requests to Dr. Philip L. Cohen, Division of Rheumatology, University of Pennsylvania, 421 Curie Boulevard, Suite 757, Philadelphia, PA 19104. E-mail address: philipco{at}mail.med.upenn.edu
3 Abbreviations used in this paper: cGVH, chronic graft-versus-host; BBS, borate-buffered saline; KO, knockout; RF, rheumatoid factor; WT, wild type.
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