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* Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA 19104;
Institute of Organ Transplantation, Sichuan Provincial People’s Hospital/Academy of Medical Sciences of Sichuan, Chengdu, China;
Ontario Cancer Institute and Department of Immunology, University of Toronto, Ontario, Canada;
Department of Laboratory Medicine and Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520; and
¶ The Wistar Institute, Philadelphia, PA 19104
Selective interference with the CD45RB isoform by mAb (anti-CD45RB) reliably induces donor-specific tolerance. Although previous studies suggest participation of regulatory T cells, a mechanistic understanding of anti-CD45RB-induced tolerance is lacking. We report herein the unexpected finding that tolerance induced by this agent is not established in B cell-deficient mice but can be recovered by preemptive B lymphocyte transfer to B cell-deficient hosts. Using B cells from genetically modified donors to reconstitute B cell-deficient recipients, we evaluate the role of B lymphocyte-expressed CD45RB, T cell costimulatory molecules, and the production of Abs in this novel tolerance mechanism. Our data document an Ab-induced tolerance regimen that is uniquely B lymphocyte-dependent and suggest mechanistic contributions to tolerance development from the B cell compartment through interactions with T cells.
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 NIH-AI 05851-01 and NIH-AI 048820-05 (to J.F.M.) from the National Institutes of Health.
2 S.D. and D.J.M. contributed equally to this study.
3 Address correspondence and reprint requests to Dr. Shaoping Deng, University of Pennsylvania, 313 Stemmler Hall, Philadelphia, PA 19104; E-mail address: dengs{at}mail.med.upenn.edu or Dr. James F. Markmann, Department of Surgery, Hospital of the University of Pennsylvania, 36th and Hamilton Walk, Philadelphia, PA 19104; E-mail address: james.markmann{at}uphs.upenn.edu
4 Current address: Department of Pediatrics, Vanderbilt University, Nashville, TN 37232.
5 Current address: National Institutes of Health/National Heart, Lung, and Blood Institute.
6 Abbreviations used in this paper: Treg, regulatory T cell; mIgM, membrane IgM; HA, hemagglutinin; MST, median survival time.
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