New insights into the development of B cell responses: Implications for solid organ transplantation

A resurgent interest in the role of B cells following solid organ transplantation is being driven by clinical data suggesting that antibody mediated rejection (AMR) is a major cause of dysfunction and organ transplant failure. These observations suggest that, in a subset of patients, current immunotherapies are failing to control the development of alloantibody responses, and/or failing to reverse the production or the effects of alloantibodies. Quantification of donor-specific antibodies (DSA) has proven to be an imperfect predictor of AMR, and efforts to improve DSA quantification anticipate that this will result in improved predictive power. At the same time, attempts to control of ABMR have focused on the non-specific elimination of B cells, plasma cells (PCs) or circulating antibodies. In the past decade, there has been an improvement in our understanding of the processes that drive B cell differentiation into germinal center (GC)-dependent or GC-independent memory B cells and antibody-secreting PC. These insights are suggesting new ways to more specifically target the DSA response, which may lead to better long-term allograft survival outcomes while preserving protective immunity. In this review, new insights into processes that lead to antibody production upon primary and secondary antigen encounter are discussed, and the potential implications to DSA production as well as future areas of investigation to control AMR are discussed.