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A new study, published in Science Advances and led by researchers at NDCN, reveals how the body fails to stop self-targeting B Cells in a rare autoimmune brain disease called CASPR2-antibody encephalitis, an illness where the body’s immune system mistakenly creates antibodies that attack a brain protein called CASPR2.
B cells are immune cells that produce antibodies. Normally, the immune system will remove B cells that can attack our own body, and the paper focused on two ‘checkpoints’ in the body where this happens.
The first checkpoint, ‘central tolerance’, eliminates harmful B cells in bone marrow. ‘Peripheral tolerance’ is the second checkpoint, which deals with escaped B cells in the body’s circulation. In patients with CASPR2-antibody encephalitis, both these checkpoints failed and allowed B cells to evolve into memory B cells. These memory cells undergo additional mutations to bind more strongly to CASPR2, enabling them to produce high-potency, disease-causing antibodies.
Using a mouse model, the team demonstrated that mature, CASPR2-specific memory B cells caused behavioural changes which mirror those seen in human CASPR2-antibody encephalitis.
Unexpectedly, researchers also found that even healthy people had early-stage B cells that can bind to CASPR2. However, in these people, the B cells were effectively blocked from becoming disease-causing memory B cells. This finding shows the critical importance of peripheral checkpoints in preventing B cell–mediated autoimmune disease.
Read the full story on the Nuffield Department of Clinical Neurosciences website.