Preprint Club
A cross-institutional Journal Club Initiative

Keywords

• T and B cell communication

• CNS autoimmunity

• Ectopic lymphoid follicle-like structures

Main Findings

In this preprint, the authors investigated the relationship of CD4 T cells and B cells in the central nervous system (CNS) during neuroinflammation. Authors used the experimental autoimmune encephalomyelitis (EAE) murine model of multiple sclerosis (MS) generated by adoptive transfer of in vitro differentiated myelin-oligodendrocyte (MOG)-specific CD4 T cells and particularly focusing on the ectopic lymphoid follicle-like structures (eLFs) that form during CNS inflammation.

First, authors showed that both in vitro differentiated MOG-specific Th1 and Th17 cells induced EAE with equivalent severity and incidence. However Th17-induced EAE was accompanied with higher levels of B cells and the formation of lager and more frequent eLFs.

Combining histological and flow cytometric analyses with single cell transcriptomics of CNS isolated cells, and intravital imaging of meningeal eLFs, the researchers evaluated T:B communication. In Th17-EAE, activated B cells and B1/Marginal Zone-like B cells were overrepresented in the CNS and authors identified B cells poised for undergoing antigen-driven germinal center (GC) reactions and clonal expansion in the CNS. Transcriptomic analyses showed that these CNS B cells had enhanced capacity for antigen presentation and immunological synapse formation. Using labelled T cells, authors visualized Th17:B cell communication in eLFs, in real-time using intravital microscopy of the CNS and demonstrated extensive communication and long-lasting contacts between T and B cells in meningeal eLFs, associated with T cell activation. Moreover, using mice devoid of B cells, authors confirmed the need for B cells to maintain a highly pro-inflammatory cytokine profile of transferred MOG-specific Th17 cells.

The data acquired, suggest that interaction of T and B cells in meningeal eLFs in Th17-EAE model not only promotes differentiation and clonal expansion of B cells, but also leads to reactivation of CNS T cells.

Limitations

• While this preprint provides important in vivo observations about the relationship between CD4 T cells and B cells in eLFs, it would also be interesting to evaluate the underlying molecular mechanisms governing these interactions.

• The authors demonstrate that B cells are needed for Th17 reactivation in the CNS. It would also be relevant to understand whether B cell depletion impact on EAE severity.

• Authors have observed in CNS a population of CD11b expressing macrophages around the eLFs. It would be interesting to extend those results and assess whether those cells are macrophages or microglia cells and their activation level by additional markers.

Significance/Novelty

CNS ectopic lymphoid structures have been shown to arise during MS pathogenesis. The results from this preprint suggest that interaction of T and B cells in meningeal eLFs in Th17-EAE model not only promotes differentiation and clonal expansion of B cells, but also leads to reactivation of CNS T cells and thereby may support inflammatory processes within the CNS.

While these findings provide valuable insights into the role of eLFs in immune responses and their potential implications for MS, further research is needed to fully understand the clinical significance of eLFs and their impact on disease progression and treatment strategies.

Credit

Reviewed by Ramojus Balevicius as part of a cross-institutional journal club between the Icahn School of Medicine at Mount Sinai, the University of Oxford, the Karolinska Institute and the University of Toronto.

The author declares no conflict of interests in relation to their involvement in the review.