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.

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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
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