Recruitment of Autoimmune B Cells in EAE
B cells and their secreted products participate in various pathogenic and regulatory immune responses, which are so far barely appreciated in experimental models. Apart from producing tissue specific autoantibodies, autoimmune B cells secrete regulatory cytokines, chemokines and growth factors, and act as specific antigen presenting cells to create particular immune milieus. Indeed, our studies of OSE and RR mice strongly suggested that bidirectional interactions between MOG-specific T and B lymphocytes act as a central element in the spontaneous pathogenesis of EAE (1, 2). We combine selective B cell depletion, two-photon microscopy and molecular techniques to address the role of B cells in distinct stages of EAE.
We found that in RR mice, MOG specific B cells are recruited from the unmodified, native B cell repertoire and that these produce demyelinating autoantibodies. Recruitment, expansion and activation of these autoimmune B cells seem to require the help by transgenic MOG specific T cells, but also the presence of CNS derived MOG. These processes happen in the germinal centers of cervical lymph nodes (Fig. 4), which are connected to the CNS by lymphatic vessels.
This system offers an unique approach to study mechanisms of spontaneous recruitment of B cells without external manipulation. The questions raised include the transport of myelin autoantigen from CNS to lymph nodes, initiation of autoantibody forming germinal centers and the selection of autoimmune B cells.
1. B. Pöllinger et al., J. Exp. Med. 206, 1303 (2009).
2. K. Berer et al., Nature 479, 538 (2011).