B cell modulation strategies in the improvement of transplantation outcomes

Successful transplantation outcome is the final goal in most end stage and nonfunctional organs; however, despite using different therapeutic strategies, antibody-mediated rejection is still a big obstacle. B cells have a key role in transplant rejection by several functions, such as antibody production, antigen presenting, contribution in T cell activation, forming the germinal center, and tertiary lymphoid organs. Therefore, B cells modulation seems to be very crucial in transplant outcome. A double-edged sword function is considered for B cells during transplantation; On the one hand, antibody production against the transplanted organ induces antibody-mediated rejection. On the other hand, IL10 production by regulatory B (Breg) cells induces graft tolerance. Nowadays, several monoclonal antibodies (mAb) are available for B cell modulation that are routinely used in transplant recipients, among which rituximab (anti-CD20 mAb) act in eliminating B cells. However, there are some other monoclonal antibodies, such as epratuzumab and Inotuzumab ozogamicin (IO), which exert anti-CD22 activity, resulting in disruption of B cell functions and induction of tolerance in autoimmune disease or B cell malignancies; that notwithstanding, these mAbs have not yet been tried in transplantation. In this review, we focus on different methods for modulating the activity of B cells as well as induction of Breg cells, aiming to prevent the allograft rejection.