In this issue of the JCI, 2 research groups developed double-transgenic mice (TCR^MOG×IgH^MOG mice, or OSE mice) expressing T and B cell receptors that recognize the same myelin protein, MOG (2, 3). More than 50% of these mice developed inflammatory demyelinating lesions in their spinal cords and optic nerves, reminiscent of human MS. The studies suggest that B cells play a critical role as APCs in OSE mice. B cells are able to present antigen efficiently because (a) the antigen receptor concentrates antigen from very low levels; (b) engagement of the antigen receptor generates signals that upregulate costimulatory molecules like CD86; and (c) antigen is shuttled to a compartment where it competes well for binding to MHC class II for presentation to T cells. Activated T cells then express the proinflammatory cytokines IFN-γ and IL-17. MOG-specific B cells were also shown to undergo class switching to IgG1 in the presence of transgenic T cells; however, this occurred in all double-transgenic mice whether they were asymptomatic or had clinical EAE, suggesting that anti-MOG IgG1 antibodies are not required to trigger disease.