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Mechanical Forces in B cell activation
The generation of protective antibodies depends on the selective expansion of B cells with the strongest binding of their B cell receptors (BCRs) to foreign antigens. This process starts by formation of B cell immune synapses with antigen-presenting cells. BCR signalling in immune synapses triggers extraction of the antigens, leading to B cell antigen processing and presentation to helper T cells – a step that ultimately controls B cell expansion. To internalise antigen from immune synapses, B cells generate forces by activating the non-muscle myosin IIa. Myosin contractility invaginates synaptic antigen clusters and promotes antigen internalisation by clathrin-mediated endocytosis. Contractile forces rupture low avidity interactions between the BCR and antigens and provide a negative feedback on BCR antigen binding and signalling. Thus, B cells use mechanical forces to test the strength of antigen binding to the BCR . The location, intensity and timing of the forces are distinctly regulated in B cell subsets. In naive B cells, antigen clusters form and grow in lamellipodia, and are gathered towards the centre of the synapse. Forces are applied at the base of lamellipodia, creating a delay that allows increase in avidity and sensitive antigen endocytosis. In contrast, germinal centre B cells apply strong forces on small antigen clusters in the periphery of the synapse. This synaptic architecture of germinal centre B cells is associated with higher stringency of affinity discrimination. Thus, B cell selection is regulated by the architecture of immune synapses through the coordination of signalling, contractility and endocytosis.
Date:
17 June 2015, 13:00
Venue:
Sir William Dunn School of Pathology, South Parks Road OX1 3RE
Venue Details:
EPA Seminar Room
Speaker:
Dr Pavel Tolar (The Frances Crick Institute)
Organising department:
Sir William Dunn School of Pathology
Organiser:
Anton van der Merwe (Sir William Dunn School of Pathology)
Host:
Anton van der Merwe (Sir William Dunn School of Pathology)
Part of:
Dunn School of Pathology Research Seminars
Booking required?:
Not required
Audience:
Public
Editor:
Anton van der Merwe
