Abstract
Meningeal ectopic lymphoid follicle-like structures (eLFs) have been described in multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE), but the cellular processes within and their role in CNS autoimmunity is not clearly understood. Here, we employed the Th17 adoptive transfer EAE model, which features formation of large, numerous eLFs, to analyze the cellular processes within these structures. We show that clusters of activated B cells and B1/Marginal Zone-like B cells are overrepresented in the CNS and identified B cells poised for undergoing antigen-driven germinal center (GC) reactions and clonal expansion in the CNS. Furthermore, we found evidence for enhanced capacity for antigen presentation and immunological synapse formation in CNS B cells. To visualize Th17:B cell communication in eLFs, we labeled Th17 cells with a ratiometric calcium sensor, allowing us to study their interactions with tdTomato-labeled B cells in real-time using intravital microscopy of the CNS. Thus, we demonstrate for the first time that there is extensive communication and long-lasting contacts between T and B cells in meningeal eLFs, and that B cells are able to reactivate T cells. Consistent with these findings, we show that CNS T cells depend on CNS B cells to maintain a highly pro-inflammatory cytokine profile. Our data suggest that interaction of T and B cells in meningeal eLFs in our model not only promotes differentiation and clonal expansion of B cells, but also leads to reactivation of CNS T cells and thereby supports smoldering inflammatory processes within the CNS. Thus, our results may provide a direction for future research into the function of eLFs in MS.
Competing Interest Statement
The authors have declared no competing interest.
