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Wiskott-Aldrich Syndrome protein deficiency perturbs the homeostasis of B-cell compartment in humans.
[wiskott-aldrich syndrome]
Wiskott-
Aldrich
Syndrome
protein
(
WASp
)
regulates
the
cytoskeleton
in
hematopoietic
cells
and
mutations
in
its
gene
cause
the
Wiskott-
Aldrich
Syndrome
(
WAS
)
,
a
primary
immunodeficiency
with
microthrombocytopenia
,
eczema
and
a
higher
susceptibility
to
develop
tumors
.
Autoimmune
manifestations
,
frequently
observed
in
WAS
patients
,
are
associated
with
an
increased
risk
of
mortality
and
still
represent
an
unsolved
aspect
of
the
disease
.
B
cells
play
a
crucial
role
both
in
immune
competence
and
self-tolerance
and
defects
in
their
development
and
function
result
in
immunodeficiency
and
/
or
autoimmunity
.
We
performed
a
phenotypical
and
molecular
analysis
of
central
and
peripheral
B-
cell
compartments
in
WAS
pediatric
patients
.
We
found
a
decreased
proportion
of
immature
B
cells
in
the
bone
marrow
correlating
with
an
increased
presence
of
transitional
B
cells
in
the
periphery
.
These
results
could
be
explained
by
the
defective
migratory
response
of
WAS
B
cells
to
SDF-
1
α
,
essential
for
the
retention
of
immature
B
cells
in
the
BM
.
In
the
periphery
,
we
observed
an
unusual
expansion
of
CD
2
1
(
low
)
B-
cell
population
and
increased
plasma
BAFF
levels
that
may
contribute
to
the
high
susceptibility
to
develop
autoimmune
manifestations
in
WAS
patients
.
WAS
memory
B
cells
were
characterized
by
a
reduced
in
Â
vivo
proliferation
,
decreased
somatic
hypermutation
and
preferential
usage
of
IGHV
4
-
34
,
an
immunoglobulin
gene
commonly
found
in
autoreactive
B
cells
.
In
conclusion
,
our
findings
demonstrate
that
WASp-
deficiency
perturbs
B-
cell
homeostasis
thus
adding
a
new
layer
of
immune
dysregulation
concurring
to
the
increased
susceptibility
to
develop
autoimmunity
in
WAS
patients
.
