ePoster Presentation 49th Annual Scientific Meeting of the Australian and New Zealand Society for Immunology 2021

Altered BAFF signalling in MS is associated with aberrant B cell homeostasis and proinflammatory activation (#213)

Jonatan Leffler 1 , Stephanie Trend 1 2 , Natalie C Ward 3 , Georges E Grau 4 , Simon Hawke 4 , Scott N Byrne 4 5 , Allan G Kermode 2 6 , Martyn A French 7 8 , Prue H Hart 1
  1. Telethon Kids Institute, Subiaco, WA, Australia
  2. Centre for Neuromuscular and Neurological Disorders, Perron Institute for Neurological and Translational Science, University of Western Australia, Perth, WA
  3. Medical School, University of Western Australia, Perth, WA
  4. The University of Sydney, Vascular Immunology Unit, School of Medical Sciences, Faculty of Medicine and Health, Sydney, NSW
  5. Westmead Institute for Medical Research, Centre for Immunology and Allergy Research, Westmead, NSW
  6. Institute for Immunology and Infectious Disease, Murdoch University, Perth, WA
  7. School of Biomedical Sciences, University of Western Australia, Perth, WA
  8. PathWest Laboratory Medicine,, Perth, WA

Multiple sclerosis (MS) is an autoimmune and neurodegenerative disease resulting in demyelination of neurons, lack of signal transmission and reduced muscular mobility. Although classically viewed as a T cell driven disease, recent findings suggest that B cells play a significant role in disease development and pathology. To further explore this, B cell profiles in peripheral blood from 28 treatment-naive MS patients were assessed using flow cytometry and compared to 17 healthy controls. Using conventional and algorithm-based analysis we observed a trend towards increased abundance of memory B cells (MBC) in MS. Further analysis revealed a significant increase of IgA+ MBC as well as minor differences in other MBC phenotypes. By screening circulating B cells for markers associated with B cell function, we discovered a significantly decreased expression of the B cell activation factor receptor (BAFF-R) in MS patients compared to controls. BAFF-R expression was negatively associated with serum levels of its ligand, suggesting that downregulation may be due to increased levels of BAFF. In healthy controls, BAFF-R expression was associated with abundance of differentiated MBC but this was not observed in MS. In MS patients, decreased BAFF-R expression correlated with increased production of proinflammatory TNF following B cell stimulation. Together, these data suggest that BAFF signalling is dysregulated in MS and may lead to aberrant MBC cell homeostasis and proinflammatory B cell activation. Previous attempts to block BAFF signalling in MS patients unexpectedly increased disease severity, suggesting that BAFF signalling contributes to MS immunopathology but that mechanisms are incompletely understood.