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.
Type
Journal articleSubject
AnimalsB-Lymphocytes
Disease Models, Animal
Graft Rejection
Humans
Isoantibodies
Macaca mulatta
Mice
Organ Transplantation
Rats
Transplantation Immunology
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https://hdl.handle.net/10161/10059Published Version (Please cite this version)
10.1016/j.smim.2011.08.022Publication Info
Kwun, Jean; Bulut, Pinar; Kim, Eugenia; Dar, Wasim; Oh, Byoungchol; Ruhil, Ravi; ...
Knechtle, Stuart J (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.
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Show full item recordScholars@Duke
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
Jean Kwun
Assistant 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.
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