Researchers at the Francis Crick Institute and Imperial
College London have discovered specialised mechanical and
signalling properties in a type of B lymphocyte -
infection-fighting cells in our immune system - called germinal
centre B cells. These newly discovered properties help to explain
how very potent antibodies are produced during an
infection.
B lymphocytes, or B cells, are a type of white blood cell that
are responsible for producing antibodies to protect us against
infectious disease or foreign invaders.
Dr Pavel Tolar of the Crick (currently based at the Mill Hill
Laboratory) said: "Germinal centres are special sites in our
lymphatic system that arise during an infection.
Germinal centres are dynamic groupings of B cells together with
helper T lymphocytes, another type of immune cell. They are
supported by specialised stromal, or connective tissue, cells that
capture pieces of the pathogen and present them to the B cells.
"Within these germinal centre structures, the B cells
proliferate, mutate their antibody genes and are selected for
improved reactivity to the pathogen. The main benefit, affinity
maturation of antibodies - where the antibodies become able to more
strongly bind to the pathogen they need to fight - is critical for
immune protection."
Germinal center B cells are rare and do not survive common cell
purification methods. This has made studying them difficult. In
this research, Dr Tolar and his colleagues developed techniques for
high-resolution microscopy of thousands of untouched and unpurified
germinal centre B cells and were able to study their cell biology
for the first time.
Dr Tolar said: "Affinity maturation in the germinal centre
depends on the ability of B cells to form contacts, or immune
synapses, with the cells presenting the foreign antigens and to
acquire these antigens for processing and presentation to helper T
cells.
"Our data show that germinal centre B cells form very unusual
immune synapses, where spread-out clusters of the antigen are
extracted from the presenting cells by strong pulling forces. The
mechanical forces enhance the ability of germinal centre B cells to
distinguish between weak and strong binding to the antigen, a
property that is expected to promote affinity maturation."
The researchers also found that after antigen binding, germinal
center B cells had reduced amounts of an important signalling
molecule that is normally required for these cells to multiply
(which is important to create a big enough 'army' of immune cells
to fight the pathogen). This fits with the idea that this final
step ultimately relies on cross-checking signals from neighbouring
helper T cells.
These strong 'tugging' mechanical forces generated by germinal
centre B cells were an unexpected player in the process of affinity
maturation. The researchers hope that their work might eventually
lead to the design of vaccines with mechanical or geometric
properties tailored to germinal centre B cells.
The paper, Germinal center B cells recognize antigen through
a specialized immune synapse architecture, is published inNature Immunology.