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Blood, 1 September 2007, Vol. 110, No. 5, pp. 1595-1602. Prepublished online as a Blood First Edition Paper on June 1, 2007; DOI 10.1182/blood-2006-12-061648. This Article Full Text Full Text (PDF) Erratum (v111,p3299) All Versions of this Article: blood-2006-12-061648v1 110/5/1595    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 Kilmon, M. A. Articles by Vilen, B. J. Search for Related Content PubMed PubMed Citation Articles by Kilmon, M. A. Articles by Vilen, B. J. Related Collections Immunobiology Phagocytes Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Macrophages prevent the differentiation of autoreactive B cells by secreting CD40 ligand and interleukin-6 Michelle A. Kilmon1, Nikki J. Wagner1, Alaina L. Garland1, Li Lin2, Katja Aviszus3, Lawrence J. Wysocki3, and Barbara J. Vilen1 Departments of1 Microbiology and Immunology, and 2 Biostatistics and Data Management, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill; 3 Integrated Department of Immunology, National Jewish Medical and Research Center and University of Colorado Health Sciences Center, Denver Activation of the innate immune system promotes polyclonal antibody secretion to eliminate invading pathogens. Inherent in this process is the potential to activate autoreactive B cells and induce autoimmunity. We showed previously that TLR-stimulated dendritic cells and macrophages regulate B cell tolerance to Smith antigen, in part through the secretion of interleukin-6 (IL-6). In this manuscript, we show that neutralization of IL-6 fails to abrogate macrophage-mediated repression and identify soluble CD40 ligand (CD40L) as a second repressive factor secreted by macrophages. CD40L selectively repressed Ig secretion by chronically antigen-experienced (anergic) immunoglobulin transgenic and nontransgenic B cells but not by transiently stimulated B cells. The importance of macrophages in maintaining B cell tolerance was apparent in lupus-prone MRL/lpr mice. Compared with C57BL/6 mice, macrophages from MRL/lpr mice were significantly less efficient at repressing immunoglobulin secretion coincident with diminished IL-6 and CD40 ligand production. These data indicate that macrophages regulate autoreactive B cells by secreting repressive factors that prohibit terminal differentiation of B cells. The regulation of autoreactive B cells by macrophages is diminished in lupus-prone mice suggesting a role in autoimmunity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: V. W.S. Lee, X. Qin, Y. Wang, G. Zheng, Y. Wang, Y. Wang, J. Ince, T. K. Tan, L. K. Kairaitis, S. I. Alexander, et al. The CD40-CD154 co-stimulation pathway mediates innate immune injury in adriamycin nephrosis Nephrol. Dial. Transplant., November 4, 2009; (2009) gfp569v1. [Abstract] [Full Text] [PDF] R. Diz, S. K. McCray, and S. H. Clarke B Cell Receptor Affinity and B Cell Subset Identity Integrate to Define the Effectiveness, Affinity Threshold, and Mechanism of Anergy J. Immunol., September 15, 2008; 181(6): 3834 - 3840. [Abstract] [Full Text] [PDF] D. O. Bunch, J. S. Silver, M. C. Majure, P. Sullivan, D. A. Alcorta, H. Chin, S. L. Hogan, Y. I. Lindstrom, S. H. Clarke, R. J. Falk, et al. Maintenance of Tolerance by Regulation of Anti-myeloperoxidase B Cells J. Am. Soc. Nephrol., September 1, 2008; 19(9): 1763 - 1773. [Abstract] [Full Text] [PDF]

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