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Title: Investigating novel components and mechanisms involved in B cell receptor-antigen internalisation
Author: Natkanski, E. M.
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2013
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The elimination of a wide variety of infections requires the production of high affinity antibodies specific for the invading pathogen. The generation of these high affinity antibodies depends on the ability of B cells to recognise and internalise antigens from the surface of antigen-presenting cells (APCs) in an affinity-dependent manner. B cells expressing high affinity B cell receptors (BCRs) internalise, process and present more antigen, obtain better T cell help, and are selectively expanded over lower affinity equivalents. However, the molecular mechanisms by which B cells extract antigens for presentation remain unclear. Using a new fluid and flexible membrane substrate to mimic APCs, we show that B cells acquire antigen by dynamic myosin IIA-mediated contractions that pull out and invaginate the presenting membranes. Invaginations containing high affinity BCR-antigen microclusters were able to withstand the force of these contractions and recruit clathrin resulting in endocytosis. In contrast, low affinity BCR-antigen bonds quickly ruptured aborting internalisation. Thus we conclude that coupling contractility to endocytosis permits B cells to discriminate between antigen affinities, which provides a mechanism for the selective advantage seen for high affinity B cell clones in vivo. Disruptions in BCR-antigen internalisation has been linked to the growth of malignant B cells and the development of autoimmunity. Therefore, ultimately, our results could contribute to the effective design of future therapeutics for B cell diseases.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available