Mechanical forces in B cell activation
Pavel Tolar PH.D.
MRC National Institute for Medical Research,
Division of Immune Cell Biology,
United Kingdom
Abstract
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 thus 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.
Time:Dec. 09th, 2014, 16:00.
Venue: New Biology Building, room 143
Host: Prof. Wanli Liu
举办单位：生命科学联合中心
