Essential role for B cells in transplantation tolerance

Abstract

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. Furthermore, the long-term survival of organ allografts remains challenged by chronic rejection, a process in which activated B cells have been found to play a significant role. Therefore, the achievement of transplantation tolerance will likely require induction of both T and B cell tolerance to alloantigens. Moreover, human and animal investigations have shown that subsets of B cells, Transitional and Regulatory, are inherently tolerogenic. Developing therapeutic strategies that exploit these populations may be key to achieving transplantation tolerance. In this review we describe the current evidence for the essential role of B cells in transplant tolerance and discuss emerging B cell directed strategies to achieve allograft tolerance.

A Case for APRIL/BLyS Directed Therapy Not Eosinophil Directed Therapy for Alloantibody Elimination

“…The presence of additional cells leading to sustained levels of APRIL, BLyS and IL-6, may explain why the authors failed to see an appreciable change in plasma cell numbers and DSA. Regardless, we concur with the authors that eosinophil directed immunotherapy is unlikely to be an effective therapy for desensitization, and that DSA directed research should focus on therapies that block downstream targets like APRIL for desensitization strategies (10 …”

Induction of Mixed Chimerism Using Combinatory Cell-Based Immune Modulation with Mesenchymal Stem Cells and Regulatory T Cells for Solid-Organ Transplant Tolerance

“…In addition to the evaluation of T-helper cell subsets and cytokine profiles, we dissected the B-cell populations affected by treatment. There is increasing evidence that B cells play a significant role in the long-term survival of allografts [44]. In the mixed chimeras, we observed significant decreases in populations of effector B cells and an increase in the frequency of IL-10-producing B cells within the mature B-cell population.…”

Lymphodepletional Strategies in Transplantation

“…Several B-cell-targeting therapeutics have emerged over the last decade, as our understanding of the impact of B cells on allograft rejection as well as transplant tolerance has increased (Redfield et al 2011;Kwun et al 2012a). These strategies may be of particular interest in the setting of T-cell depletion in which humoral immunity is often up-regulated.…”