The coin toss of B cells in rejection and tolerance: Danger versus defense

Transplantation is the preferred therapy for the end stage organ disease. Since the introduction of organ transplantation into medical practice in 1953 [1], significant progress has been achieved in patient and graft survival rates due to improvements in surgical techniques and more targeted immunosuppressive medications [2]. Nevertheless, current gaps in the management of the transplant patient stem from an incomplete understanding about the heterogeneity of the injury response in organ transplantation, at different rates and different time points after transplantation, as well as our inability to monitor the immunologic threshold of risk versus safety in each individual patient. Recent advances in immunology/transplantation biology with the advent of high throughput “omic” assays such as gene microarrays, proteomics, metabolomics, antibiomics, chemical genomics and functional imaging with nanoparticles, offers us unique methods to interrogate and decipher the variability and unpredictability of the immune response in organ transplantation (Fig. 1) [3]. Recent studies using these applications [3], [4], [5], [6], [7] and [8] have uncovered a critical and pivotal role for specific B cell lineages in organ injury [9] and organ acceptance [10] and [11] (Fig. 2). The availability of specific therapies against some of these defined B cell populations provides for an exciting new field of B cell targeted manipulation that can both abrogate the allospecific injury response, as well as promote allospecific graft accommodation and health.

► High throughput assays provide necessary pathogenic mechanistic insights of B cell biology in organ transplantation.
► Specific B cell lineages are involved in transplant rejection and tolerance.
► Targeted B cell therapy may potentially be an exciting new field of treatment for acute rejection episodes.