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#Post#: 982--------------------------------------------------
B cells can drive inflammation in MS
By: agate Date: October 23, 2015, 3:20 pm
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Indexed but not abstracted in PubMed, October 23, 2015. The
article below is from The Scientist (October 21):
[quote]B Cells Can Drive Inflammation in MS
Researchers identify a subset of proinflammatory
cytokine-producing B cells that may spark multiple
sclerosis-related inflammation.
By Anna Azvolinsky | October 21, 2015
A type of B cell that produces the inflammation-inducing
cytokine granulocyte macrophage–colony stimulating factor
(GM-CSF) may be key to driving disease-causing inflammation and
relapses in multiple sclerosis (MS), according to research
published today (October 21) in Science Translational Medicine.
The results of the study, in which researchers examined blood
samples from MS patients, suggest a possible mechanism as to why
B cell-targeted therapies have been found to be efficacious for
the disease.
“This is an important paper and among the first to study the
role of B cells in MS, which has predominantly been studied from
a T cell perspective,” said Claudia Mauri, a professor of
immunology at the University College London who was not involved
in the work.
In MS, immune cells attack the protective myelin coating that
surrounds nerve fibers that branch out from neurons, leading to
difficulties in walking and balance, muscle spasms, numbness,
and other symptoms resulting from faulty communication between
the central nervous system (CNS) and the rest of the body. Among
the cells of the adaptive immune system implicated in the
disease, T cells have been most studied because they outnumber B
cells in MS lesions and because of their dominant role in
experimental autoimmune encephalomyelitis, the most commonly
used mouse model of the human disease.
Previously, antibody-mediated depletion of B cells was shown to
reduce new inflammation in patients with relapsing MS. Recent
clinical trial results showed that the anti-CD20 antibody,
ocrelizumab, significantly reduced new CNS inflammation and
relapse in MS patients and progression in those with gradually
worsening disease. “The [positive results] of this antibody
treatment are surprising and this paper may show why this
treatment works so well in people,” said Ari Waisman, a
professor at the Medical University of Mainz in Germany, who
penned an accompanying perspective.
While B cells are best known for making antibodies, the benefit
of B cell depletion in limiting MS relapse is likely unrelated
to this function since the abnormal antibodies present in the
spinal fluid of MS patients do not change following the
effective B cell depletion therapy, according to study coauthor
Amit Bar-Or, a neurologist and neuroimmunologist at the Montreal
Neurological Institute and Hospital in Canada. To study the role
of B cells in MS beyond antibody generation, Bar-Or and his
colleagues analyzed B cells extracted from blood draws of 35 MS
patients and 35 healthy volunteers. The researchers identified a
population of memory B cells that expressed GM-CSF and were more
frequent and active in the blood MS patients compared to that of
controls. These B cells derived from MS patients could also
stimulate a switch in macrophages to become proinflammatory,
which is thought in turn to activate MS-promoting T cells.
In the blood of MS patients, depleting B cells with another
anti-CD20 antibody, rituximab, resulted in detection of more
macrophages that were anti- rather than proinflammatory.
Sampling blood in these patients after their B cell pool had
been repopulated revealed both a persistent reduction in the
number of detected GM-CSF producing B cells and an
anti-inflammatory effect on macrophages suggesting a shift in
the balance between anti- and proinflammatory immune cells that
might provide a benefit for MS patients. “It appears that in
addition to removing pro-inflammatory B cells, both the B cells
generated after therapy and the macrophages are less
inflammatory,” Bar-Or told The Scientist.
The team also uncovered the signaling mechanism that underlies
the generation of the GM-CSF expressing B cells, which could be
useful for identifying targeted approaches to selectively
inhibit these cells, according to Bar-Or.
While these cells appear to play a potentially important role in
the disease, these results do not show that these B cells are
pathogenic or causative in MS, Anne Cross, a professor of
neurology at the Washington University School of Medicine in St.
Louis who studies the pathology of MS using mouse models but was
not involved in the work, noted in an email.
The study raises many questions on the pathogenesis of MS and
immune function in general. Cross said she would like to see
whether the disproportionate presence of this GM-CSF-producing B
cell subset may be a general characteristic of other autoimmune
or inflammatory diseases. Bar-Or and his colleagues plan to
investigate this question, as well as whether these cells may be
a useful biomarker for MS relapse.
Another question, according to Mauri, is whether these newly
identified cells produce other cytokines and signaling
molecules. How these B cells potentially influence the activity
of MS-promoting T cells is also not clear. “The immune system is
very complex. All cells communicate and influence each other in
a tissue-dependent way,” said Mauri. “This study should raise
more interest for other researchers to study the role of B cells
in immune diseases.”
_______________________
R. Li et al., “Pro-inflammatory GM-CSF–producing B cells in
multiple sclerosis and B cell depletion therapy,” Science
Translational Medicine, doi:10.1126/scitranslmed.aab4176,
2015.[/quote]
The article can be seen here
HTML http://www.the-scientist.com/?articles.view/articleNo/44289/title/B-Cells-Can-Drive-Inflammation-in-MS/.
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