021 – Investigating the role of cytokine-producing B cells in initiation and regulation of EAE
Anna Sophie Thomann (1) – Katarina Pinjušic (2) – Anneli Peters (1)
Institute of Clinical Neuroimmunology, University Hospital and Biomedical Center, Ludwig-Maximilians-Universitt Mnchen, Munich, Germany (1) – Department of Neuroimmunology, Max Planck Institute of Neurobiology, Martinsried, Germany (2)
Multiple sclerosis (MS) is a an autoimmune, inflammatory disease in which the immune system attacks the myelin sheath of the central nervous system (CNS) leading to tissue inflammation, massive demyelination, axonal damage and loss. Although MS is a quite common disease affecting almost 2.5 million people worldwide, MS pathogenesis is still not fully understood. Originally, Th1 and Th17 cells were thought to be the main drivers of CNS tissue inflammation and demyelination in MS and its mouse model experimental autoimmune encephalomyelitis (EAE). However, increasing evidence suggests also a role of B cells in disease pathogenesis. Clinical data indicate that B cells contribute to disease initiation and progression through antigen-presentation and cytokine production, possibly by promoting differentiation of specific pathogenic T cell subsets such as Th1 or Th17 cells. The aim of this study is to investigate how cytokine production by antigen-specific B cells can shape the T cell response in EAE. We have found that B cells specific for the CNS antigen MOG produce more pro-inflammatory and less anti-inflammatory cytokines indicating a pathogenic potential of these B cells. Furthermore, we have established an in vitro culture system for the retroviral transduction of B cells allowing for both the overexpression and knock-down of different cytokines in B cells. Using this culture system in combination with different EAE mouse models, we will be able to investigate whether antigen-specific B cells can support or suppress differentiation of pathogenic T cell subsets via cytokine production. This will shed light on the relevance of antigen-presentation and cytokine production by antigen-specific B cells for disease initiation and progression and help to understand the relationship between B cells and different T cell subsets in EAE and MS.