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Blood, 1 July 2004, Vol. 104, No. 1, pp. 115-122. Prepublished online as a Blood First Edition Paper on March 4, 2004; DOI 10.1182/blood-2003-07-2456. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-07-2456v1 104/1/115    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 Hausl, C. Articles by Reipert, B. M. Search for Related Content PubMed PubMed Citation Articles by Hausl, C. Articles by Reipert, B. M. Related Collections Hemostasis, Thrombosis, and Vascular Biology Immunobiology Transfusion Medicine Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Preventing restimulation of memory B cells in hemophilia A: a potential new strategy for the treatment of antibody-dependent immune disorders Christina Hausl, Rafi U. Ahmad, Hans Peter Schwarz, Eva M. Muchitsch, Peter L. Turecek, Friedrich Dorner, and Birgit M. Reipert From BioMolecular Therapeutics (BMT) Research, Vienna, Austria; Technical University, Vienna, Austria; and Baxter BioScience, Vienna, Austria Memory B cells are responsible for the rapidly emerging antibody response after antigen reexposure. The signals required for the restimulation of memory B cells have not been fully explained. We used a murine model of anti–factor VIII (FVIII) antibody responses in hemophilia A to study the requirements for the restimulation of FVIII-specific memory B cells and their differentiation into anti-FVIII antibody-producing cells. We were particularly interested in the significance of activated T cells and costimulatory interactions. Our results indicate that the restimulation of FVIII-specific memory B cells is strictly dependent on interactions with activated T cells. These activated T cells can be specific for either FVIII or third-party antigens. Restimulation by T cells specific for third-party antigens requires the presence of FVIII, indicating that signals induced by B-cell receptor (BCR) triggering and by interactions with activated T cells are important. The blockade of B7-1 or B7-2 as well as the blockade of CD40L inhibits the restimulation and differentiation of FVIII-specific memory B cells in vitro and in vivo. The interference with inducible costimulator–inducible costimulator ligand (ICOS-ICOSL) interactions, however, does not cause any modulation. As expected, the production of anti-FVIII antibodies by plasma cells is not dependent on any of the costimulatory interactions tested. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Rafei, J. Hsieh, S. Fortier, M. Li, S. Yuan, E. Birman, K. Forner, M.-N. Boivin, K. Doody, M. Tremblay, et al. Mesenchymal stromal cell-derived CCL2 suppresses plasma cell immunoglobulin production via STAT3 inactivation and PAX5 induction Blood, December 15, 2008; 112(13): 4991 - 4998. [Abstract] [Full Text] [PDF] B. Peng, P. Ye, B. R. Blazar, G. J. Freeman, D. J. Rawlings, H. D. Ochs, and C. H. Miao Transient blockade of the inducible costimulator pathway generates long-term tolerance to factor VIII after nonviral gene transfer into hemophilia A mice Blood, September 1, 2008; 112(5): 1662 - 1672. [Abstract] [Full Text] [PDF] S. Lacroix-Desmazes, A.-M. Navarrete, S. Andre, J. Bayry, S. V. Kaveri, and S. Dasgupta Dynamics of factor VIII interactions determine its immunologic fate in hemophilia A Blood, July 15, 2008; 112(2): 240 - 249. [Abstract] [Full Text] [PDF] P. Allacher, C. Hausl, R. U. Ahmad, H. P. Schwarz, P. L. Turecek, and B. M. Reipert Toll-Like Receptor Triggering Modulates Factor VIII-Specific Immune Memory in Murine Hemophilia A with Factor VIII Inhibitors. Blood (ASH Annual Meeting Abstracts), November 16, 2005; 106(11): 214 - 214. [Abstract] C. Hausl, R. U. Ahmad, M. Sasgary, C. B. Doering, P. Lollar, G. Richter, H. P. Schwarz, P. L. Turecek, and B. M. Reipert High-dose factor VIII inhibits factor VIII-specific memory B cells in hemophilia A with factor VIII inhibitors Blood, November 15, 2005; 106(10): 3415 - 3422. [Abstract] [Full Text] [PDF] C. Hausl, R. U. Ahmad, M. Sasgary, C. B. Doering, P. S. Lollar, G. Richter, H. P. Schwarz, P. L. Turecek, and B. M. Reipert Inhibition of Factor VIII-Specific Memory B Cell Responses by Supra-Physiological Concentrations of Factor VIII. Blood (ASH Annual Meeting Abstracts), November 16, 2004; 104(11): 38 - 38. [Abstract]

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