The role of B cells in solid organ transplantation.

Abstract

The role of antibodies in chronic injury to organ transplants has been suggested for many years, but recently emphasized by new data. We have observed that when immunosuppressive potency decreases either by intentional weaning of maintenance agents or due to homeostatic repopulation after immune cell depletion, the threshold of B cell activation may be lowered. In human transplant recipients the result may be donor-specific antibody, C4d+ injury, and chronic rejection. This scenario has precise parallels in a rhesus monkey renal allograft model in which T cells are depleted with CD3 immunotoxin, or in a CD52-T cell transgenic mouse model using alemtuzumab to deplete T cells. Such animal models may be useful for the testing of therapeutic strategies to prevent DSA. We agree with others who suggest that weaning of immunosuppression may place transplant recipients at risk of chronic antibody-mediated rejection, and that strategies to prevent this scenario are needed if we are to improve long-term graft and patient outcomes in transplantation. We believe that animal models will play a crucial role in defining the pathophysiology of antibody-mediated rejection and in developing effective therapies to prevent graft injury. Two such animal models are described herein.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1016/j.smim.2011.08.022

Publication Info

Kwun, Jean, Pinar Bulut, Eugenia Kim, Wasim Dar, Byoungchol Oh, Ravi Ruhil, Neal Iwakoshi, Stuart J Knechtle, et al. (2012). The role of B cells in solid organ transplantation. Semin Immunol, 24(2). pp. 96–108. 10.1016/j.smim.2011.08.022 Retrieved from https://hdl.handle.net/10161/10059.

This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.

Scholars@Duke

Kwun

Jean Kwun

Associate Professor in Surgery

Research interests include humoral tolerance to organ transplants in animal model and humans, developing a clinically relevant animal model to study the mechanisms of antibody-mediated rejection (AMR), and establishing a conceptual basis that will translate into therapeutic intervention of AMR.

Knechtle

Stuart Johnston Knechtle

William R. Kenan, Jr. Distinguished Professor

During my career as an academic surgeon, I have had the privilege of leading and/or participating in a diverse portfolio of hypothesis-driven research projects.  These projects have centered on the immunology of surgery and transplantation, including both cellular and antibody-mediated immune responses.  During my training I studied the response of hyper-sensitized recipients to allogeneic liver transplantation, and am currently studying means of reducing immunologic memory that might allow more successful transplantation in sensitized recipients.  This immune response involves pathways of coagulation, antibody-mediated rejection, and cellular rejection and current work in my lab involves these three pathways.  The other major focuses of my work have been co-stimulation blockade and immune cell depletion as approaches to immunologic unresponsiveness or tolerance.  My research group has been involved in translational and clinical research to develop these mechanistic tools for the benefit of human organ transplant recipients.

Recent Publications

Knechtle SJ, Shaw JM, Hering BJ, Kraemer K, Madsen JC. Translational impact of NIH-funded nonhuman primate research in transplantation. Sci Transl Med. 2019 Jul 10;11(500). pii: eaau0143. Reprint | Full Text


Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.