Transplant immunologists at the Houston Methodist Research Institute will receive about $1.6 million over four years from the National Institute of Allergy and Infectious Diseases to study pathological antibodies produced from activated memory B cells during the chronic rejection of organ transplants.
The project, led by Roger Sciammas, Ph.D., builds on recent work that shows the antibodies produced by memory B cells in the body's response to perceived foreign material -- such as an organ or tissue donated from another person -- depends on molecular switches. Sciammas and co-principal investigator and University of Chicago transplant biologist Anita Chong, Ph.D., will use single-cell tracking and advanced genetic techniques to learn more about these regulators.
Of particular interest is whether these switches can in turn be therapeutically targeted in a way that improves organ transplant tolerance.
Although immunosuppression dampens the immune response to a transplanted organ, it is clear that current drug modalities are insufficient to achieve tolerance. When rejection occurs, memory B cell activation and antibodies are a common denominator.
The scientists will also examine whether and how memory B cell function is affected by T cell costimulation blockade, a major immunosuppression treatment widely used in experimental transplantation.
"These studies will provide new insight into the associations of alloantibody and increased incidence of transplant rejection as well as into new immunosuppressive strategies to control B cells and their antibody products," Sciammas said.
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