1. Interleukin 5 immunotherapy depletes alloreactive plasma cells.

    Journal of Surgical Research 187(1):310 (2014) PMID 24267616

    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...
  2. Interleukin 5 immunotherapy depletes alloreactive plasma cells

    Journal of Surgical Research 187(1):310 (2014)

    Background 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 inhibiti...
  3. Murine islet allograft tolerance upon blockade of the B-lymphocyte stimulator, BLyS/BAFF.

    Transplantation 93(7):676 (2012) PMID 22262127

    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 ...
  4. New wine in old bottles: expanding roles for B cells in transplantation tolerance.

    Seminars in Immunology 24(2):75 (2012) PMID 22483169

  5. Primary B cell repertoire remodeling to achieve humoral transplantation tolerance

    Seminars in Immunology 24(2):109 (2012)

    Highlights ► T- and B-lymphocyte acceptance of alloantigen is critical for transplantation tolerance. ► Recent studies suggest purging alloreactive B cells at the time of transplantation is effective. ► Following B cell depletion, newly emerging Transitional B cells may impar...
  6. Primary B cell repertoire remodeling to achieve humoral transplantation tolerance.

    Seminars in Immunology 24(2):109 (2012) PMID 21978627

    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 ...
  7. New wine in old bottles: Expanding roles for B cells in transplantation tolerance

    Seminars in Immunology 24(2):75 (2012)

  8. Essential role for B cells in transplantation tolerance.

    Current Opinion in Immunology 23(5):685 (2011) PMID 21982511

    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...
  9. Strategies for B-lymphocyte repertoire remodeling in transplantation tolerance.

    Immunologic Research 51(1):1 (2011) PMID 21948256

    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...
  10. Acquisition of humoral transplantation tolerance upon de novo emergence of B lymphocytes.

    Journal of Immunology 186(1):614 (2011) PMID 21084661

    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 ...
  11. Essential role for B cells in transplantation tolerance

    Current Opinion in Immunology 23(5):685 (2011)

    Highlights ► Transplantation tolerance requires a tolerant B cell compartment. ► B cells as antigen-presenting cells can impact T cell function both in a positive as well as a negative manner. ► Transitional B cells and B regulatory cells are emerging as playing a crucial role in B cel...
  12. B-lymphocyte homeostasis and BLyS-directed immunotherapy in transplantation.

    Transplantation Reviews 24(4):207 (2010) PMID 20655723 PMCID PMC2946495

    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...
  13. 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) PMID 20387063 PMCID PMC2875467

    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...
  14. Interleukin 5 immunotherapy depletes alloreactive plasma cells

    Journal of Surgical Research (2009)

    Background 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 inhibiti...
  15. In vivo BLyS/BAFF neutralization ameliorates islet-directed autoimmunity in nonobese diabetic mice.

    Journal of Immunology 181(11):8133 (2008) PMID 19018006 PMCID PMC2586964

    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...
  16. B lymphocyte-directed immunotherapy promotes long-term islet allograft survival in nonhuman primates.

    Nature Medicine 13(11):1295 (2007) PMID 17965721

    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...
  17. B cell-mediated antigen presentation is required for the pathogenesis of acute cardiac allograft rejection.

    Journal of Immunology 177(11):7715 (2006) PMID 17114442

    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...
  18. Cutting edge: impaired transitional B cell production and selection in the nonobese diabetic mouse.

    Journal of Immunology 176(12):7159 (2006) PMID 16751358

    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...
  19. The frequency of double-positive thymocytes expressing an alphabeta TCR clonotype regulates peripheral CD4 T cell compartment homeostasis.

    Immunology 116(3):400 (2005) PMID 16236130 PMCID PMC1802421

    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...
  20. NOD B-cells are insufficient to incite T-cell-mediated anti-islet autoimmunity.

    Diabetes 54(7):2019 (2005) PMID 15983202

    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 ...