Francis Crick Institute scientists have discovered that immune
cells called B cells use mechanical forces to physically pull
antigens such as viruses or toxins from the surfaces of other
cells.
The work was carried out by Katelyn Spillane and Pavel Tolar of
the Crick. Dr Tolar explains: "Long-term protection against
infectious diseases requires the production of highly potent
antibodies by B lymphocytes, or B cells.
"B cell responses start when they encounter foreign antigens on
the surfaces of a type of immune cell called antigen-presenting
cells. The B cell and the antigen-presenting cell form a tight
contact, known as an immune synapse, from which the B cell can
acquire the antigen for processing and presentation to helper T
cells so it can be destroyed.
"To produce highly potent antibodies, B cells need to select the
antigens that they bind to strongly."
Studying how B cells acquire antigens from the surfaces of other
cells is difficult using traditional experimental approaches. This
led the researchers to develop new DNA-based nanosensors that,
combined with fluorescence imaging, allowed them to visualise how
the process happens.
They discovered that the mechanical forces B cells generate to
physically pull antigens from the surface of antigen-presenting
cells cause B cells to respond differently based on the stiffness
of the antigen-presenting cell. The scientists suggest that B cell
responses, and therefore the production of potent antibodies during
infection, may be supported by the physical properties of the
immune cells involved.
Dr Tolar says: "Our work suggests that it should be possible to
actively control B cell responses by manipulating physical cues
received in the immune synapse. We hope that this research might
eventually lead us to design and engineer vaccines with physical
properties tailored to elicit the production of desired antibodies,
for example by using nanoparticles of different stiffness."
The paper, B cell antigen extraction is regulated by physical
properties of antigen presenting cells, is published in theJournal of Cell Biology.