Researchers have uncovered new details about how the immune system prevents the production of antibodies that can recognise and damage healthy tissues.
Some B cells generate antibodies that recognise “self-antigens” produced by the body’s own cells, potentially causing the immune system to attack healthy tissues by mistake, leading to a variety of autoimmune diseases.
To help stop this, the immune system tries to eliminate self-reactive B cells by exposing them to self-antigens as they develop in the bone marrow.
This process is thought to be controlled by B cell receptors (BCRs) on the surface of the developing B cells.
In the new study, research teams from Yale and Stanford report that this process also depends on a receptor called TLR9. This receptor is located inside B cells in compartments known as late endosomes and is activated by binding to fragments of DNA.
The researchers discovered that depleting TLR9 impairs central tolerance and causes mice to produce increased numbers of self-reactive B cells and antibodies. They found that TLR9 activity is also reduced in the B cells of patients with the autoimmune disease systemic sclerosis. Similar decreases in TLR9 activity have previously been observed in lupus patients’ B cells.
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