Long-term Survival of Transplanted Islets by Targeting B Cells Rather than T cells

JDRF-funded researchers have shown that a treatment that specifically targets and depletes B cells can promote the survival of transplanted islets in diabetic nonhuman primates. Many factors are involved in socalled islet graft failures, including recurring autoimmunity and strong immune responses to the transplanted tissue. While most researchers have focused on therapeutics targeting the body’s T cells, Ali Naji and colleagues from the JDRF/University of Pennsylvania Islet Transplantation Center in Philadelphia have demonstrated that B cells are also important contributors to islet transplant failure. The discovery suggests that future tolerance induction strategies should include both B cell and T cell–directed agents. The induction therapy used in this research comprised two separate antibody preparations: a broad antibody treatment called ATG, made up of a diverse repertoire of antibodies; and the monoclonal antibody rituximab, which binds to a protein widely expressed on B cells. The development of antibodies against the donor islets was stopped only with continued rituximab monotherapy. The study is reported in the journal Nature Medicine.