Intracellular sorting receptor, SorLA, regulates antigen trafficking, processing and presentation in B cells

Intracellular sorting receptor, SorLA, regulates antigen trafficking, processing and presentation in B cells

Dr Dessi Malinova; Queen’s University Belfast

Dessi is an immunologist and cell biologist interested in the molecular mechanisms of immune cell function. She completed her PhD in Molecular Immunology at UCL Great Ormond Street Institute of Child Health. Her doctoral thesis, under the supervision of Prof Adrian Thrasher, focused on elucidating how immune cells interact to mount an effective immune response, quantifying distinct actin networks at antigen driven cell-cell contacts and elucidating mechanistic details of several primary immunodeficiencies related to actin dysregulation. Dessi joined the MRC National Institute for Medical Research, later Francis Crick Institute, as a postdoctoral researcher in Prof Pavel Tolar’s lab, where she continued to study adaptive immunity, particularly B cell activation and antibody responses. This led to the characterisation of novel endocytic pathways for antigen-triggered B cell receptors. In 2020, Dessi joined the Wellcome-Wolfson Institute for Experimental Medicine as a Patrick G Johnston Fellow to establish her independent research in immune cell receptor activation in health and disease. Her research programme has attracted funding from the Royal Society, Medical Research Council, Higher Education Authority and Leukaemia and Lymphoma NI.

Antigen uptake and presentation has a central role in B-cell mediated immunity but few molecular details have been elucidated. Through unbiased screening we have identified signalling and intracellular trafficking regulators with a clear role in B cell antigen processing and germinal centre formation upon immunological challenge in vivo. Using microscopy, antigen degradation and presentation assays we have identified a novel role for the retrograde trafficking receptor, SorLA, in BCR trafficking. SorLA disruption reduced degradation of BCRantigen complexes and eventual antigen presentation. We are currently investigating how these processes contribute to progression of B cell malignancies.

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