A rare type of B cell that naturally acts to dampen T cell immune responses could feasibly be exploited as a form of cell immunotherapy for autoimmune disorders, scientists report. Researchers at Duke University Medical Center and the National Heart, Lung, and Blood Institute have identified how to expand IL-10-secreting B cells ex vivo, and demonstrated that transferring some of these cells into a mouse model of multiple sclerosis-like autoimmune disease significantly reduces symptoms. They report their research in Nature, in a paper titled “Regulatory B cells control T-cell autoimmunity through IL-21-dependent cognate interactions.”
Prior work has identified a population of IL-10-secreting regulatory B cells in mice and humans. In healthy animals these cells are very rare, but expand under conditions of autoimmunity, and can negatively regulate inflammation and autoimmune disease as well as innate and antigen-specific adaptive immune responses. What hasn’t been clear to date, however, is how B10-cell IL-10 production and regulation of antigen-specific immune responses are controlled in vivo without inducing systemic immunosuppression.
The investigators, led by Duke professor of immunology Thomas A. Tedder, Ph.D., have now shown that B10 cell expansion and maturation into functional IL-10-secreting effector cells that inhibit in vivo autoimmune disease requires stimulation by IL-21 and CD40-dependent cognate interactions with T cells. Applying the right triggers to B10 cells isolated from wild-type mice and cultured in vitro led to up to 4 million-fold expansion. Transferring just some of these expanded cells back into mice with experimental autoimmune encephalomyelitis resulted in significant suppression of disease.
“Regulatory B cells are a fairly new finding that we’re just beginning to understand,” professor Tedder explains. “B10 cells are important because they make sure an immune response doesn’t get carried away, resulting in autoimmunity or pathology. This study shows for the first time that there is a highly controlled process that determines when and where these cells produce IL-10 ... This research shows that we may have the potential to unharness regulatory cells, make millions of copies, and introduce them back into someone with autoimmune disease to shut down the disease.”