We followed with great interest the “Cutting Edge” contribution by Faunce et al. (1) reporting bovine myelin basic protein (MBP) induced experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. In response, Furlan (2) noted that C57BL/6 (H2b) mice are traditionally considered resistant to MBP-EAE induced by standard immunization protocols.
We have recently been able to induce MBP-EAE in C57BL/6 mice using rat MBP and a boost protocol, in which mice were immunized s.c. with 200 μg rat MBP in CFA on days 0 and 17 followed by standard pertussis toxin (3). This protocol results in a monophasic, moderate disease course starting around day 20 with the histopathological hallmarks of inflammation and axonal damage, but no significant demyelination. In our hands, immunization with guinea pig or murine MBP instead of rat MBP was not successful.
Other known protocol modifications leading to MBP-induced EAE in H2b mice include combination of active and passive immunization, coinjection of IFN-γ (4), and ultra-high doses of encephalitogen or adjuvants. The latter seems to be the case in the present study by Faunce et al., which uses 400 μg of encephalitogen and 4 mg/ml CFA.
Therefore, we do not share Furlan’s surprise about the results reported from Dr. Streilein’s laboratory. Rather, it seems likely that selection of the appropriate Ag and immunization protocol forcing a vigorous Th1 shift can overcome resistance to specific encephalitogens in seemingly insusceptible mouse strains.