Primary B cell repertoire remodeling to achieve humoral transplantation tolerance

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 graft survival. Thus, achieving robust transplantation tolerance will require induction of tolerance in both the T- and B-cell compartments. Here we propose that the natural developmental propensity of the B-lymphocyte compartment acquisition of tolerance to self-antigens can be recapitulated to achieve humoral transplantation tolerance. It is our contention B-lymphocyte directed induction immunotherapy would be an important component of emerging strategies for induction of Transplantation tolerance.

► 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 impart allograft tolerance.
► Stringent selection, under BLyS-limiting conditions, may promote tolerance.