Tragedy, Trade-offs, and the Demise of Morcellation.
New England Journal of Medicine 374(26):2605 (2016)
Interleukin 5 immunotherapy depletes alloreactive plasma cells.
Journal of Surgical Research 187(1):310 (2014)
Long-lived plasma cells (PCs) that form after alloantigen sensitization produce donor-specific alloantibodies that generate a positive serum crossmatch and preclude transplantation. New approaches for desensitization, including PC depletion with proteasome inhibition, show promise but carry cons...
Murine islet allograft tolerance upon blockade of the B-lymphocyte stimulator, BLyS/BAFF.
Transplantation 93(7):676 (2012)
Immunologic rejection is a major barrier to successful long-term outcomes in clinical transplantation. The importance of B lymphocytes-and their secretory products, alloantibodies-in the pathogenesis of allograft rejection is accepted. Furthermore, it is now clear that the dominant regulator of ...
New wine in old bottles: expanding roles for B cells in transplantation tolerance.
Seminars in Immunology 24(2):75 (2012)
Primary B cell repertoire remodeling to achieve humoral transplantation tolerance.
Seminars in Immunology 24(2):109 (2012)
The current mainstay of immunotherapy in clinical transplantation is T lymphocyte directed. However, it has long been appreciated that the emergence of an alloimmune response mounted by the B lymphocyte compartment and detectable as donor-specific antibodies is a critical challenge to long-term ...
Underutilization of A2 ABO incompatible kidney transplantation.
Clinical Transplantation 26(3):489 (2012)
ABO compatibility creates a disadvantage for O and B renal allograft candidates. A2 ABO incompatible transplant may decrease waiting times and generate equivalent graft survival to an ABO compatible transplant.
Death-censored graft survival was compared between A recipients and O, B, and AB reci...
Strategies for B-lymphocyte repertoire remodeling in transplantation tolerance.
Immunologic Research 51(1):1 (2011)
Transplantation tolerance remains an elusive goal as B-cell-initiated chronic humoral rejection evades current immunosuppression. B-cell-directed therapy is thus emerging as a key component in achieving transplantation tolerance and long-term graft survival. Here, we propose strategies of B-cell...
Essential role for B cells in transplantation tolerance.
Current Opinion in Immunology 23(5):685 (2011)
T lymphocytes are the primary targets of immunotherapy in clinical transplantation. However, B lymphocytes are detrimental to graft survival by virtue of their capacity to present antigen to T cells via the indirect pathway of allorecognition and the generation of donor specific alloantibody. Fu...
Acquisition of humoral transplantation tolerance upon de novo emergence of B lymphocytes.
Journal of Immunology 186(1):614 (2011)
A major obstacle to transplantation tolerance is humoral immunity. In this paper, we demonstrate that the intrinsic developmental propensity of the B lymphocyte compartment for acquisition of self-tolerance can be harnessed to induce humoral unresponsiveness to transplanted alloantigens. In the ...
B-lymphocyte homeostasis and BLyS-directed immunotherapy in transplantation.
Transplantation Reviews 24(4):207 (2010)
Current strategies for immunotherapy after transplantation are primarily T-lymphocyte directed and effectively abrogate acute rejection. However, the reality of chronic allograft rejection attests to the fact that transplantation tolerance remains an elusive goal. Donor-specific antibodies are c...
A novel CD93 polymorphism in non-obese diabetic (NOD) and NZB/W F1 mice is linked to a CD4+ iNKT cell deficient state.
Immunogenetics 62(6):397 (2010)
In the present study, we characterize a polymorphism in the CD93 molecule, originally identified as the receptor for the C1q complement component (i.e., C1qRp, or AA4.1) in non-obese diabetic (NOD) mice. This allele carries a coding polymorphism in the first epidermal growth factor-like domain o...
In vivo BLyS/BAFF neutralization ameliorates islet-directed autoimmunity in nonobese diabetic mice.
Journal of Immunology 181(11):8133 (2008)
B lymphocytes are required for the pathogenesis of autoimmune diabetes in NOD mice. Previous studies established that a lymphopenic transitional (TR) B cell compartment reduces the competitive constraint on the entry of newly emerging TR B cells into the splenic follicle (FO), thereby disrupting...
B lymphocyte-directed immunotherapy promotes long-term islet allograft survival in nonhuman primates.
Nature Medicine 13(11):1295 (2007)
We found that an induction immunotherapy regimen consisting of rabbit anti-thymocyte globulin (Thymoglobulin) and the monoclonal antibody to CD20 rituximab (Rituxan) promoted long-term islet allograft survival in cynomolgus macaques maintained on rapamycin monotherapy. B lymphocyte reconstitutio...
B cell-mediated antigen presentation is required for the pathogenesis of acute cardiac allograft rejection.
Journal of Immunology 177(11):7715 (2006)
Acute allograft rejection requires the activation of alloreactive CD4 T cells. Despite the capacity of B cells to act as potent APCs capable of activating CD4 T cells in vivo, their role in the progression of acute allograft rejection was unclear. To determine the contribution of B cell APC func...
Cutting edge: impaired transitional B cell production and selection in the nonobese diabetic mouse.
Journal of Immunology 176(12):7159 (2006)
Developing B cells undergo selection at multiple checkpoints to eliminate autoreactive clones. We analyzed B cell kinetics in the NOD mouse to establish whether these checkpoints are intact. Our results show that although bone marrow production is normal in NOD mice, transitional (TR) B cell pro...
The frequency of double-positive thymocytes expressing an alphabeta TCR clonotype regulates peripheral CD4 T cell compartment homeostasis.
Immunology 116(3):400 (2005)
The present study aimed to determine whether the frequency of double positive (DP) thymocytes expressing alphabeta T-cell receptor (TCR) clonotypes at the time of selection regulates peripheral CD4 T-cell compartment size. Scid recipients were inoculated with various ratios of TCR Calpha(0/0) an...
NOD B-cells are insufficient to incite T-cell-mediated anti-islet autoimmunity.
Diabetes 54(7):2019 (2005)
Although it is well established that B-cells are required for the development of diabetes in the nonobese diabetic (NOD) mouse, the nature of their role remains unknown. Herein, we investigate the hypothesis that B-cells in this autoimmune background actively disrupt the tolerant state of those ...
Alloreactive CD4 T cell activation in vivo: an autonomous function of the indirect pathway of alloantigen presentation.
Journal of Immunology 171(12):6502 (2003)
Activation of alloreactive CD4 T cells occurs via the direct and indirect pathways of alloantigen presentation. A novel TCR/alloantigen transgenic system was designed that permitted in vivo visualization of CD4 T cell priming through these pathways. When both pathways of alloantigen presentation...
Specialized CC-chemokine secretion by Th1 cells in destructive autoimmune myocarditis.
Journal of Autoimmunity 21(4):295 (2003)
T helper (Th) 1-mediated immune responses are associated with adverse outcomes in a number of models of autoimmune disease. Previous work has focused on the role that cytokines secreted by Th1 cells play in mediating pathologic tissue injury. To evaluate other mechanisms by which Th1 cells may b...
The role of t/b lymphocyte collaboration in the regulation of autoimmune and alloimmune responses.
Immunologic Research 27(2-3):443 (2003)
The present review highlights the two areas of research pursuit in our laboratory: (1). the regulation of the autoimmune T cell response to pancreatic islet beta cells using the nonobese diabetic (NOD) mouse model of type 1 diabetes and (2). the regulation the T cell response to alloantigens. Ou...