B-cell immunotherapeutics: emerging roles in solid organ transplantation

The introduction of B-cell-directed therapies for autoimmune diseases illuminated the biologic relevance of B cells in mediation of autoimmunity. They have also rejuvenated interest in how B cells mediate multiple effector functions that include antibody production, antigen presentation to T cells, costimulation and the production of immune stimulating and immune modulatory cytokines. These advances clearly have implications for patients receiving solid organ transplants, especially those who are ABO incompatible, sensitized to human leukocyte antigen (HLA) pretransplant, or develop anti-HLA antibodies posttransplant.

Here, we will review the current and evolving agents developed for B-cell depletion or modulation and discuss their potential for modification of alloimmunity in transplant recipients. We will focus on data from humans and animal models in which B cells and antibodies are targeted to reduce inflammation in transplantation. This will include a review of the immunomodulatory drug intravenous immunoglobulin, anti-CD20 (rituximab) where more clinical experience has been reported. Finally, we will discuss emerging B-cell-directed therapies which include those directed at the B-cell activating factor of the tumor necrosis family/A proliferation inducing ligand, anti-CD22, newer anti-CD20 monoclonals and antibodies to the interleukin 6 receptor (tocilizumab).

The primary objective of this review is to define the critical role of B cells in development of alloimmunity and how this can be modified by B-cell-directed therapies.