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Blood, 1 August 2006, Vol. 108, No. 3, pp. 974-982. Prepublished online as a Blood First Edition Paper on April 4, 2006; DOI 10.1182/blood-2005-12-006858. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2005-12-006858v1 108/3/974    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Qian, Y. Articles by Clarke, S. H. Search for Related Content PubMed PubMed Citation Articles by Qian, Y. Articles by Clarke, S. H. Related Collections Apoptosis Immunobiology Phagocytes Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Autoreactive MZ and B-1 B-cell activation by Faslpr is coincident with an increased frequency of apoptotic lymphocytes and a defect in macrophage clearance Ye Qian, Kara L. Conway, Xiangdong Lu, Heather M. Seitz, Glenn K. Matsushima, and Stephen H. Clarke From the Department of Microbiology and Immunology, the Department of Biochemistry and Biophysics, UNC Neuroscience Center, University of North Carolina, Chapel Hill, NC. Murine autoreactive anti-Smith (Sm) B cells are negatively regulated by anergy and developmental arrest, but are also positively selected into the marginal zone (MZ) and B-1 B-cell populations. Despite positive selection, anti-Sm production occurs only in autoimmune-prone mice. To investigate autoreactive B-cell activation, an anti-Sm transgene was combined with the lpr mutation, a mutation of the proapoptotic gene Fas (Faslpr), on both autoimmune (MRL) and nonautoimmune backgrounds. Faslpr induces a progressive and autoantigen-specific loss of anti-Sm MZ and B-1 B cells in young adult Faslpr and MRL/Faslpr mice that does not require that Faslpr be B-cell intrinsic. This loss is accompanied by a bypass of the early pre–plasma cell (PC) tolerance checkpoint. Although the MRL bkg does not lead to a progressive loss of anti-Sm MZ or B-1 B cells, it induces a robust bypass of the early pre-PC tolerance checkpoint. Faslpr mice have a high frequency of apoptotic lymphocytes in secondary lymphoid tissues and a macrophage defect in apoptotic cell phagocytosis. Since Sm is exposed on the surface of apoptotic cells, we propose that anti-Sm MZ and B-1 B-cell activation is the result of a Faslpr-induced defect in apoptotic cell clearance. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Z. K. Wen, W. Xu, L. Xu, Q. H. Cao, Y. Wang, Y. W. Chu, and S. D. Xiong DNA hypomethylation is crucial for apoptotic DNA to induce systemic lupus erythematosus-like autoimmune disease in SLE-non-susceptible mice Rheumatology, December 1, 2007; 46(12): 1796 - 1803. [Abstract] [Full Text] [PDF] H. M. Seitz, T. D. Camenisch, G. Lemke, H. S. Earp, and G. K. Matsushima Macrophages and Dendritic Cells Use Different Axl/Mertk/Tyro3 Receptors in Clearance of Apoptotic Cells J. Immunol., May 1, 2007; 178(9): 5635 - 5642. [Abstract] [Full Text] [PDF]

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