Multiple sclerosis (MS) is an enigmatic autoimmune disorder characterized by on-and-off neurological attacks with variable symptoms. On page 1303, Pöllinger et al. describe a new transgenic mouse model of MS that more closely mimics the human disease than many existing EAE models.
T cells in these transgenic mice (dubbed “RR” mice) recognize an epitope from the myelin protein MOG. The mice spontaneously developed EAE with relapsing-remitting attacks on different CNS tissues. Most existing EAE models, on the other hand, rely on immunization with CNS-derived antigens in adjuvant or injection of autoreactive T cells.
As occurs in MS, the RR mice developed variable symptoms. Motor problems and an unsteady gait might dominate the first attack, with paralysis dominating the next. CNS lesions in these mice contained autoantibody-producing B cells along with IL-17– and IFN-g–producing T cells. And the expression of these cytokines correlated with phases of attack and remission. Whether or not these waves were a cause or consequence of inflammation remains unknown.
B cells were critical for disease development in the new model. A role for MOG-specific B cells has also been shown in other EAE models, but the RR mice are the first to activate autoreactive B cells from the endogenous repertoire (rather than a transgene). Once triggered, the B cells produced anti-MOG antibodies that, along with complement, destroyed MOG-expressing cells in vitro. The fact that transgenic RR mice with a healthy nervous system also developed anti-MOG autoantibodies suggests that antibody production precedes overt disease.
Transgenic T cells that access the CNS might create immunogenic conditions that recruit endogenous autoreactive B cells. Or, the authors propose, MOG-containing myelin debris could be transported by phagocytes from the brain to lymph nodes, where natural, MOG-specific B cells then get activated with help from transgenic T cells.
