Plasma cell biology: principles for therapeutic design.

Plasma cells represent the terminally differentiated cell population of the B-lymphocyte lineage. Plasma cells possess a unique biology, primarily as a result of their role as antibody factories. The unique features associated with the massive antibody production capacity confer upon the plasma cell a vulnerability to attack by specific targeted therapies. Over the past nine years, we have worked to develop therapies that exploit the unique features of plasma cells - therapies we have termed plasma cell targeted therapies. To date, these therapies have been almost exclusively based on proteasome inhibitor therapy, which has been used to treat antibody-mediated rejection and also to reduce chronic human leukocyte antigen antibody production via therapies commonly referred to as "desensitization." Future iterations of plasma cell targeted regimens, however, are more likely to depend on combination therapies designed specifically to achieve additivity and preferably synergy, using either small molecule inhibitors of metabolic pathways or alternatively, biologic agents. As such, these plasma cell targeted therapies provide a new approach for treating acute and chronic antibody responses in humans, not only in transplantation, but also in other disease states including autoimmune disease.