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.