Amyloid fibrils activate B-1a lymphocytes to ameliorate inflammatory brain disease

IL-10-secreting B lymphocytes and peritoneal macrophages are activated by immunization with amyloid fibrils composed of short peptides resulting in reduction of paralysis and inflammation in mice with experimental autoimmune encephalomyelitis. B-cell-deficient μMT mice and IL-10 knockout animals were used to establish the critical role of regulatory B cells in the therapeutic mode of action. Reintroduction of B-1a lymphocytes into the μMT animals reconstituted the ability of the fibrils to ameliorate the paralytic signs, leading to the trafficking of both populations of cells from the peritoneum to secondary lymph organs and not to the CNS. The reduction in CNS inflammation, combined with successful intranasal administration, provides support that this strategy could be translated into an effective human therapeutic.