Induction of a regulatory B cell population in experimental allergic encephalomyelitis by alteration of the gut commensal microflora.

We have recently shown that alteration of the gut commensal microbiota with antibiotics can modify the susceptibility to autoimmune demyelinating processes of the central nervous system. Treatment of mice with a broad spectrum of antibiotics not only induced significant changes in the regulatory T cell populations of the gut associated lymphoid tissues (GALT) and peripheral lymphoid organs but reduced the susceptibility to EAE, the most widely used animal model for human multiple sclerosis. Here, we show further that oral antibiotic treatment of EAE mice induced a CD5(+)B cell subpopulation that conferred protection against the disease. Protection was associated with an enhanced frequency of CD5(+)B cells in distal lymphoid sites such as cervical LN. In vitro stimulation with LPS increased the production of IL-10 by splenic CD5(+)B cells. Adoptive transfer of CD5(+)B cells from antibiotic treated mice reduced significantly the severity of EAE by shifting the immune responses from Th1/Th17 towards anti-inflammatory Th2-type responses. Our results demonstrate that this specific B cell population appears to be involved in the immune regulation of autoimmunity, in particular this experimental demyelinating disease of the central nervous system by gut commensal microflora.