Historically, multiple sclerosis (MS) has been viewed as being primarily driven by T cells. However, the effective use of anti-CD20 treatment now also reveals an important role for B cells in MS patients. The results from this treatment put forward T-cell activation rather than antibody production by B cells as a driving force behind MS. The main question of how their interaction provokes both B and T cells to infiltrate the CNS and cause local pathology remains to be answered. In this review, we highlight key pathogenic events involving B and T cells that most likely contribute to the pathogenesis of MS. These include (1) peripheral escape of B cells from T cell-mediated control, (2) interaction of pathogenic B and T cells in secondary lymph nodes, and (3) reactivation of B and T cells accumulating in the CNS. We will focus on the functional programs of CNS-infiltrating lymphocyte subsets in MS patients and discuss how these are defined by mechanisms such as antigen presentation, co-stimulation and cytokine production in the periphery. Furthermore, the potential impact of genetic variants and viral triggers on candidate subsets will be debated in the context of MS.

Additional Metadata
Keywords CD8+ T cells, Epstein-Barr virus, genetic risk, germinal center, IFN-γ, T-bet+ B cells, Th1/Th17, transmigration
Persistent URL dx.doi.org/10.3389/fimmu.2020.00760, hdl.handle.net/1765/127333
Journal Frontiers in Immunology
Citation
van Langelaar, J. (Jamie), Rijvers, L. (Liza), Smolders, J. (Joost), & van Luijn, M.M. (2020). B and T Cells Driving Multiple Sclerosis: Identity, Mechanisms and Potential Triggers. Frontiers in Immunology (Vol. 11). doi:10.3389/fimmu.2020.00760