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Multiple sclerosis: proinflammatory GM-CSF-producing B cells and B cell depletion therapy


Modern scientific understanding has considered multiple sclerosis to be a disease controlled by the T cell, a type of white blood cell. Research has shown that in multiple sclerosis, T cells inappropriately attack myelin, the protective layer of fat covering nerves in the central nervous system, exposing them to damage.

Emerging studies have also discovered that B cells, another type of white blood cells that had previously been overlooked in multiple sclerosis, are significant contributors to the disease.
Recent clinical trials revealed that B cell depletion therapy ( BCDT ) in people with relapsing-remitting multiple sclerosis led to dramatic decreases in new disease activity.
But how B cells contribute to the disease and the molecular mechanisms involved in the benefit of B cell depletion therapy has not been fully elucidated.

The study, published in the Science Translational Medicine, provides groundbreaking insight into the role of B cells and their complex interaction with other immune cells in the context of multiple sclerosis.

Some B cells have been shown to promote inflammation, while others are actually able to limit inflammation. The study has implicated a subset of B cells, the GM-CSF producing B cells, as a key contributor in the pro-inflammatory immune cells responses at play in multiple sclerosis.

The study first examined samples of patients with multiple sclerosis comparing them to healthy subjects. Researchers discovered that GM-CSF producing B cells were more frequent and more prone to activation in patients with multiple sclerosis. This subset of B cells was able to activate pro-inflammatory responses of myeloid cells of the immune system Confirming these results in patients, the researchers found that after B cell depletion therapy, the myeloid cells became much less pro-inflammatory, suggesting that B cell depletion therapy may work in part by decreasing the number of GM-CSF-producing B cells and in turn limiting both myeloid cell and T cell contribution to new disease activity.

The study is significant in discovering a new way by which B cells can contribute to abnormal immune responses in multiple sclerosis which reinforces the rationale for the use of B cell depletion therapy.
A selectively targeting of distinct B cell populations is important because B cells normally play key roles in the immune system. ( Xagena )

Source: McGill University, 2015

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